Diabetes Ther (2024) 15:2001–2025

https://doi.org/10.1007/s13300-024-01628-0

REVIEW

Medication‑Induced Hyperglycemia and Diabetes

Mellitus: A Review of Current Literature and Practical
Management Strategies
Akshay B. Jain · Valerie Lai

Received: May 20, 2024 / Accepted: July 15, 2024 / Published online: July 31, 2024
© The Author(s) 2024

ABSTRACT certain types of medication-induced hypergly-

cemia. In this review, we will discuss the evi-
dence behind the main classes of medications
that cause hyperglycemia, their mechanism of
With the increasing global incidence of diabe-
action, specific agents that are associated with
tes mellitus, physicians may encounter more
worsened glycemic control, and, most impor-
patients with acute and chronic complications
tantly, management strategies that are tailored
of medication-induced hyperglycemia and dia-
to each specific class.
betes. Moreover, medication-induced diabetes
may be an important contributing factor to
the high rates of diabetes, and recognizing its
impact and risk is a critical step in curtailing its Keywords: Medication; Hyperglycemia;
effect on the global population. It has long been Diabetes mellitus; Drug induced hyperglycemia;
recognized that multiple classes of medications Steroid hyperglycemia; Drug-induced diabetes
are associated with hyperglycemia through vari-
ous mechanisms, and the ability to foresee this
and implement adequate management strategies
are important. Moreover, different antihypergly-
cemic medications are better suited to combat
the hyperglycemia encountered with differ-
ent classes of medications, so it is critical that
physicians can recognize which agents should
be used, and which medications to avoid in

A. B. Jain (*)
Division of Endocrinology, Department of Medicine,
University of British Columbia, Vancouver, BC,
Canada
e-mail: oxyjain@gmail.com
V. Lai
Division of Endocrinology and Metabolism,
Department of Medicine, University of Calgary,
Calgary, AB, Canada

Vol.:(0123456789)
2002 Diabetes Ther (2024) 15:2001–2025

INTRODUCTION
Key Summary Points
The global prevalence of diabetes is estimated
The exact incidence of medication-induced at 10.5% in 2021 in those aged 20–79 years old,
hyperglycemia and diabetes is unknown, but and is projected to rise to 12.2% in 2045, affect-
there is evidence that glucocorticoids, antip- ing approximately 783.2 million people by then
sychotic medications, cardiovascular medica- [1].
tions (statins, beta blockers, diuretics), certain Drugs used in the management of various
anti-infectives, antineoplastic medications, conditions can sometimes lead to impairment
immunosuppressive agents, and hormonal of glucose homeostasis, leading to abnormally
treatment are associated with changes in elevated blood glucose or worsening of previ-
glucose metabolism and increased incidence ously existent diabetes mellitus (Fig. 1). These
of hyperglycemia and/or diabetes. commonly include medications such as glu-
The main mechanisms of medication- cocorticoids, antipsychotics, thiazides, statins,
induced hyperglycemia include insulin resist- antineoplastic agents, and beta blockers. As
ance, weight gain, and direct effect on beta such, patients requiring these medications are
cell action, but certain medications alter glu- at high risk of developing medication-induced
cose metabolism in other specific ways which diabetes.
can change management, and are important The importance of monitoring for and rec-
to recognize. ognizing medication-induced hyperglycemia
is significant. Certain medications (e.g., anti-
Assessment of underlying patient risk factors,
neoplastic treatment, immunosuppression in
dose and duration of a medication that can
inflammatory conditions) require long-term
cause hyperglycemia or diabetes, and pre-
use and have benefits that potentially outweigh
existing comorbidities (e.g., cardiovascular
the risks of hyperglycemia. Moreover, adequate
disease, renal disease) are key factors to evalu-
management of hyperglycemia could allow for
ate risk of medication-induced hyperglycemia
continuation of these agents. However, if left
and diabetes, and a frank discussion with the
unrecognized and/or untreated, both acute and
patient regarding these risks is warranted.
chronic (including micro- and macrovascular)
Patient education, discussion of glucose mon- complications of hyperglycemia can arise [2].
itoring, involvement of allied health care, The exact incidence and prevalence of
and ensuring that all members of the health drug-induced hyperglycemia and diabetes are
care team (including physician prescribing unknown as a result of limited studies, the
hyperglycemia-inducing medication and sometimes transient nature of hyperglycemia
physician responsible for managing diabetes, with resolution upon discontinuation of the
if different) are aware of hyperglycemia risks implicated medication, the lack of distinguish-
are critical factors to ensure proper manage- ing features between naturally occurring versus
ment. medication-induced diabetes, and the lack of
Management of medication-induced hyper- monitoring and testing [3]. In addition, many
glycemia generally includes lifestyle meas- individuals may have undiagnosed diabetes that
ures and if required, pharmacologic treat- comes to light when there is further worsening
ment (with metformin generally first line). of hyperglycemia due to use of such medica-
Depending on factors discussed in this tions. Finally, the occurrence of hyperglycemia
review, addition of other antidiabetes medi- and/or diabetes following the initiation of an
cations may also be required. implicated medication can range from days to
years [2], with the dose and duration of treat-
ment also affecting the probability of hypergly-
cemia. As a general overview, LaPreze and Robin-
son have reported the incidence of drug-induced
Diabetes Ther (2024) 15:2001–2025 2003

Fig. 1  The main mechanisms of medication-induced inhibitors, TKI tyrosine kinase inhibitor, PI3K phospho-
hyperglycemic based on medication class. GC gluco- inositide 3-kinase, AKT protein kinase B, CNI calcineurin
corticoids, AP antipsychotics, BB beta blockers, PI pro- inhibitors, SSA somatostatin analogue, ADT androgen
tease inhibitor, mTORi mammalian target of rapamycin deprivation therapy, IFN-A interferon alpha

diabetes or hyperglycemia to be 40–65% with GLUCOCORTICOIDS

glucocorticoid use, 10–30% with antipsychotic
use, 3–17% with antiretroviral use, 0.8–1.9% Current Evidence
with immune checkpoint inhibitors use, 63%
with alpelisib use, 15–30% in transplant immu- Perhaps the most well-known class of medica-
nosuppression use, 10% with thiazide diuretic tion that leads to hyperglycemia and diabetes
use, 7–48% in statin use, 6.8–19.8% in niacin is glucocorticoids. A meta-analysis (N = 34,907)
use, and 22% with beta blocker use [4]. We rec- by Liu et al. reports that glucocorticoid-induced
ognize that lack of robust, prospective, and ran- hyperglycemia and diabetes occur at a rate of
domized trials proving causality can often lead 32.3% (p = 0.003) and 18.6% (p = 0.002), respec-
to wide variability of incidence with certain tively, in patients without pre-existing diabe-
medications (e.g., statin therapies). Important tes [5]. On a global level, glucocorticoid use is
considerations when evaluating medication- linked to 2% of new-onset diabetes mellitus [6].
induced hyperglycemia are shown in Table 1. Another study found that in a hospitalized pop-
We would like to elaborate on some of these ulation receiving high dose glucocorticoids, 56%
considerations with the following medications of patients without diabetes developed hypergly-
implicated in leading to hyperglycemia, both cemia (defined as blood glucose ≥ 11.1 mmol/L
well-known as well as newer therapies. or 200 mg/dL) [7]. Furthermore, the incidence of
This article is based on previously conducted glucocorticoid-induced diabetes mellitus is likely
studies and does not contain any new studies underreported as a result of the use of fasting
with human participants or animals performed blood glucose instead of postprandial/random
by any of the authors. blood glucose as glucocorticoids typically cause
elevated postprandial blood glucose values [8].
2004 Diabetes Ther (2024) 15:2001–2025

Table 1  Different aspects of medication-induced hyperglycemia

Risk factors/patient characteristics Drugs implicated Management considerations
Pre-existing diabetes Glucocorticoids Mechanism of action of impaired glucose
homeostasis
Impaired fasting glucose Antipsychotics Dose of implicated drug leading to
hyperglycemia
Impaired glucose tolerance family history Beta blockers Duration of treatment with implicated
of diabetes drug leading to hyperglycemia
Personal history of GDM (gestational Thiazide diuretics Potential for altered nutritional intake
diabetes mellitus) on therapy
BMI > 27 Statins Renal and hepatic function
Abdominal obesity Antibiotioics (gatifloxacin) Absolute or relative contraindications
for use of antihyperglycemic therapy
Age Antivirals (protease inhibitors, Individualized glycemic targets
nucleoside reverse transcriptase
inhibitors)
Antineoplastic medications Side effects associated with antihyper-
glycemic therapy
Immunosuppression Frequency of self-monitoring of blood
glucose
Somatostatin analogues
Androgen deprivation therapy
Interferon alpha
Thyroid hormone
Diazoxide
Phenytoin
Teprotumumab

Mechanism of Action the liver to further accelerate gluconeogene-

sis. Hepatic insulin resistance is another criti-
Glucocorticoid-induced hyperglycemia is medi- cal mechanism. Normally, insulin suppresses
ated via binding of glucocorticoid receptors gluconeogenesis, but in the presence of gluco-
within hepatic, adipose, skeletal, and pancre- corticoids, gluconeogenesis is allowed to con-
atic tissue [8]. Within the liver, glucocorticoids tinue despite presence of insulin [11]. At the
upregulate the enzymes involved in gluconeo- skeletal muscle level, glucocorticoids inhibit
genesis [8]. Gluconeogenic precursors such as glucose transporter type 4 (GLUT4) recruit-
amino acids from protein catabolism [9] and ment, thereby decreasing glucose uptake into
fatty acids from lipolysis [10] get delivered to skeletal muscle [12]. Glucocorticoid effects on
increased central obesity, increased hepatic ste-
atosis due to increased lipolysis, and increased
Diabetes Ther (2024) 15:2001–2025 2005

appetite stimulation all contribute to the devel- postprandial glucose after lunch has been sug-
opment of steroid-induced hyperglycemia and/ gested as offering the highest diagnostic sensitiv-
or diabetes [8]. ity, especially with the use of intermediate-acting
glucocorticoids such as prednisone [18]. Shorter
Different Agents courses and smaller doses of glucocorticoids in
patients with minimal risk factors who are not
All routes of glucocorticoid use are associated critically ill may be managed with non-insulin
with increased risk of hyperglycemia at high agents such as metformin or sulfonylureas [19].
doses, but oral routes of administration confer Dipeptidyl peptidase 4 (DPP4) inhibitors have
a high risk of hyperglycemia [8]. Commonly been shown in a small study to reduce the mean
used oral glucocorticoids include prednisone, amplitude of glycemic excursions in a popula-
prednisolone, and dexamethasone. Although tion who developed glucocorticoid-induced dia-
worsening of hyperglycemia can occur even at betes [20]. Similarly, there is a paucity of high-
physiologic replacement doses of glucocorti- quality studies showing adequate effect with
coids, the risk increases as the dose of gluco- sodium glucose co-transporter 2 (SGLT2) inhibi-
corticoids increases. It is thought that the risk tors in this setting. One study showed that the
particularly increases at a glucocorticoid dose use of dapagliflozin did not result in better gly-
equivalent to prednisone 7.5 mg/day [13]. A cemic control compared to placebo in patients
systematic review reported an even higher risk with prednisone-induced hyperglycemia during
of hyperglycemia with intravenous steroids acute exacerbation of chronic obstructive pul-
compared to oral steroids, with an odds ratio monary disease (AECOPD) [21]. Diabetes Can-
of 2.39 (95% CI 1.16–4.91) [14]. Inhaled gluco- ada also has a list of sick day medications that
corticoids (e.g., fluticasone > 1000 μg/day) have should be held when an individual is acutely
been reported to increase the incidence of dia- ill, which includes SGLT2 inhibitors [22]. Fur-
betes mellitus by 34% [15]. Another study dem- thermore, the Joint British Diabetes Societies
onstrated that intra-articular steroid injections for inpatient care have published consensus
may cause hyperglycemia and generally occurs guidelines for management of hyperglycemia
within 24–72 h [16]. Andersen et al. reported a and steroid therapy, and state that there is no
positive link between topical steroids and the evidence for SGLT2 inhibitors in steroid-induced
incidence of type 2 diabetes mellitus (T2DM) hyperglycemia [23]. Considering the evidence,
that was dose related with an adjusted hazard we feel that the use of SGLT2 inhibitors may
ratio of 1.27 (95% CI 1.26–1.29) [17]. not be appropriate in most settings where glu-
cocorticoids are used for a short duration for the
management of acute sickness. Typically, if the
Management duration of glucocorticoid use is longer, or the
patient has a history of poorly controlled diabe-
Successful management of steroid-induced tes, or is critically ill, then insulin therapy is per-
hyperglycemia begins with appropriate monitor- haps the best option to manage elevated blood
ing of blood glucose. Capillary glucose measure- glucose levels, as it offers significant efficacy and
ments can be used but have limitations includ- considerable flexibility. Glucocorticoids gener-
ing pain, frequent monitoring in some patients, ally increase postprandial compared to fasting
and potential to miss glycemic excursions. The blood glucose, so selection of the type of insu-
advent of continuous glucose monitors may lin to match the pharmacokinetics of glucocor-
be a useful alternative. Glucose monitoring ticoids is important. The use of insulin NPH or
should not be limited to fasting blood glucose insulin detemir matches the glucose profile of
and should ideally be measured postprandially prednisone, whereas longer-acting insulins such
given that glucocorticoids tend to cause post- as insulin glargine can match the longer-acting
prandial hyperglycemia [18]. Specifically, the duration of dexamethasone [19]. Initiation of
prandial insulin using regular insulin or shorter-
acting insulin analogues should be considered
2006 Diabetes Ther (2024) 15:2001–2025

if one has predominantly postprandial hyper- resistance, weight gain, and beta cell dysfunc-
glycemia despite optimization with the above tion and apoptosis [29]. Insulin resistance can
[19]. Although pre-mixed insulin can also be an occur independently of weight gain by interfer-
option, the lack of flexibility in addressing post- ing with GLUT4 translocation to the membrane
prandial hyperglycemia with these insulins can in skeletal cells [30]. The underlying mecha-
be a challenge, in our opinion. Lifestyle manage- nism for weight gain is thought to be caused
ment is also the cornerstone of managing ster- by increased appetite and food consumption
oid-induced hyperglycemia, and involving allied via acting at the serotonergic 5-HT 2C recep-
health including consultation with a dietician tor, the histaminergic ­H1 receptor, muscarinic
and diabetes nurse educator for patient educa- M3 receptors, and dopaminergic D2 receptors
tion is of significant value. Development of new [31–34]. Direct effects on pancreatic beta cells
medications that can disconnect the hyperglyce- due to increased apoptosis [35] in addition to
mic effects from the anti-inflammatory effects is impaired beta cell response to changes in blood
challenging but currently being investigated [8]. glucose [34] also contribute to antipsychotic-
induced hyperglycemia, and this occurs most
commonly with clozapine and olanzapine [36].
ANTIPSYCHOTIC MEDICATIONS
Different Agents
Current Evidence
Hyperglycemia is most common with typical
The prevalence of diabetes in patients taking antipsychotics such as haloperidol and chlor-
antipsychotics is estimated to be 20%, which promazine; however, agents such as clozapine
is 2–3 times greater than the general popula- and olanzapine, which belong to the atypical
tion [24]. A study of almost 346,000 patients in antipsychotic class, can result in significantly
Denmark by Kessing et al. reported that patients worsened obesity, weight gain, insulin resist-
taking first- or second-generation antipsychot- ance, and diabetes [29, 37]. In addition, a sys-
ics had an incident rate of diabetes of 53% and tematic review by Taylor et al. showed that all
32%, respectively, and long-term follow-up atypical antipsychotics except ziprasidone have
showed increased risk with number of antip- been associated with weight gain [38]. Aripipra-
sychotic prescriptions received in addition to zole and lurasidone also show less effect on gly-
the number of antipsychotics used [25]. When cemic disturbances [39].
compared to non-users of antipsychotics, first-
and second-generation antipsychotics had a haz-
ard ratio of 1.53 (95% CI 1.49–1.56) and 1.32 Management
(95% CI 1.22–1.24) for new-onset diabetes. In
pediatric populations, the risk of diabetes mel- Prevention of antipsychotic-induced diabe-
litus increased by threefold in children and ado- tes mellitus should first be considered, if pos-
lescents treated with antipsychotic drugs [26]. sible, given the above evidence that certain
Moreover, weight gain is estimated to occur in as agents may confer much less risk. As such, in
many as 20–50% of patients using antipsychot- patients with many risk factors, consideration
ics [27], especially with olanzapine and clozap- can be given to using ziprasidone, aripiprazole,
ine, which may further worsen hyperglycemia or lurasidone first. Non-pharmacologic manage-
[28]. ment with healthy diet and regular exercise is
also always recommended [40]. With use of the
higher-risk antipsychotics such as olanzapine or
Mechanism of Action clozapine, close monitoring of glycemic status
should be initiated, and any evidence of hyper-
Three main mechanisms are responsible glycemia and/or weight gain should be promptly
for antipsychotic-induced diabetes: insulin addressed as they may lead to non-compliance
Diabetes Ther (2024) 15:2001–2025 2007

[29]. Specifically, fasting serum glucose has and decreased insulin sensitivity [49]. A system-
been recommended to be measured annually atic analysis of eight prospective randomized
in patients starting on antipsychotic medica- controlled trials revealed that body weight was
tion [28]. In those with increased risk factors, increased in patients using beta blockers com-
fasting serum glucose can be obtained at the pared to controls, with a median difference of
3- and 6-month mark of antipsychotic use for 1.2 kg [50] which can further worsen insulin
closer monitoring [28]. Metformin, in addition resistance. Other mechanisms that contribute
to standard diabetes management, is also the include decreased first-phase insulin secretion,
mainstay of managing antipsychotic-induced which is known to be a key factor in develop-
hyperglycemia [41]. Liraglutide was also shown ment of T2DM [47, 51]. There is also evidence
to improve glucose tolerance in patients taking regarding the implications of changes in periph-
clozapine or olanzapine, and 63.8% of patients eral blood flow with beta blocker use. In healthy
with prediabetes eventually had restoration of individuals, insulin increases blood flow and
normal glucose tolerance [42], with added ben- improves delivery of substrate to skeletal muscle
efits of weight loss and reduced waist circum- and enhances glucose uptake [52]. Beta blocker
ference. A case series of patients with antipsy- use increases total peripheral resistance which
chotic-associated weight gain showed successful impedes substrate delivery, and further contrib-
weight loss with the use of once weekly low dose utes to the unwanted metabolic effects of beta
semaglutide; however, statistically significant blocker use [52].
reduction in fasting glucose and A1c were not
seen [43]. More research in the form of rand- Different Agents
omized control trials is warranted regarding the
potential use of potent incretin therapies includ- Certain beta blockers contribute to worsened
ing dulaglutide, semaglutide, and tirzepatide in hyperglycemia due to their intrinsic vasocon-
this population. strictive properties. Non-selective beta blockers
that act on beta-2 receptors prevent vasodilation
and reduce delivery of glucose to target tissue,
BETA BLOCKERS leading to decreased glucose uptake. Vasodila-
tory beta blockers that have additional alpha-1
Current Evidence blocking activity such as carvedilol are shown
to possibly improve insulin sensitivity due to
In a prospective study of 12,550 patients with- the increased glucose delivery to target tissues as
out diabetes, Gress et al. studied the incidence opposed to other agents such as metoprolol that
of new-onset diabetes and found a 28% higher have less vasodilatory effect [52]. Atenolol seems
risk after adjusting for other risk factors [44]. to have a worsened risk of incident diabetes [48].
Two other studies showed that the addition of
atenolol or propranolol to a thiazide diuretic Management
increased incident diabetes by 40% [45, 46].
Treatment with metoprolol and atenolol has also Lifestyle changes and education should be
been shown to result in elevated fasting glucose implemented in all patients, especially consid-
levels [47]. Another meta-analysis showed that ering the weight gain seen with beta blocker use.
beta blocker use led to a 22% increased risk for Limiting high doses of beta blockers or combin-
new-onset diabetes mellitus [48]. ing treatment with other agents such as cal-
cium channel blockers may also be helpful [49].
Mechanism of Action Choosing third-generation beta blockers such as
carvedilol may also be implemented [53]. Other
Hyperglycemia induced by beta blockers is antihypertensives such as angiotensin-convert-
thought to be due to weight gain, inhibition ing enzyme inhibitors (ACEI) or angiotensin
of beta-2 adrenergic-mediated insulin release, receptor blockers (ARBs) may also be added on
2008 Diabetes Ther (2024) 15:2001–2025

as combination treatment instead of increas- (including potential use of potassium supple-

ing the dose of beta blockers, as they have not mentation, if needed) is recommended. Diuretic-
shown to have any effect on glycemic regulation induced hyperglycemia is also dose dependent,
[54]. Another large meta-analysis showed that so using the lowest effective dose or combining
the lowest risk for incident diabetes was with with other first-line antihypertensives such as
ACE inhibitors and ARBs, followed by calcium calcium channel blockers, ACE inhibitors, or
channel blockers [55]. ARBs should also be considered [2]. As always,
lifestyle measures should also be implemented.

THIAZIDE DIURETICS
STATINS
Current Evidence
Current Evidence
The ALLHAT trial found that the incidence of
diabetes was significantly increased (48%) in the The incidence of diabetes mellitus was estimated
chlorthalidone group compared to lisinopril use to be between 9% and 12% with statin use in a
[56]. A meta-analysis reported that thiazide diu- recent meta-analysis [61]. Another meta-analy-
retics increased fasting plasma glucose compared sis showed a significant increase (25%) in the
to non-thiazide agents or placebo, although the incidence of new diabetes mellitus with rosuv-
mean difference was relatively small at 4.8 mg/ astatin 20 mg daily compared to placebo [62].
dL or 0.27 mmol/L [57]. Shafi et al. reports that The JUPITER trial reported similar findings, with
the risk of chlorthalidone was twice as high incident diabetes occurring more frequently in
compared to placebo, with a number needed to the rosuvastatin arm (hazard ratio 1.25 [95% CI
harm of 29 (95% CI 17–60) over 1 year, but there 1.05–1.49, p = 0.01]) [63]. The number needed
was no further risk afterwards [58]. to harm per year ranged from 125 to 250 in a
meta-analysis [64], and in another study com-
Mechanism of Action paring risk of incident diabetes to cardiovascular
events [65], the number needed to treat per year
Diuretic use commonly causes hypokalemia, to prevent one myocardial infarction is 39, so
which then results in a reduction of insulin the benefit of statin use on cardiovascular out-
secretion [58]. Other mechanisms that have comes greatly outweighs risk [64].
been suggested are related to increases in free
fatty acid levels which decrease insulin secretion Mechanism of Action
in response to glucose, significant reduction in
insulin sensitivity, and enhanced hepatic gluco- The main cause of statin-induced hyperglyce-
neogenesis in addition to catecholamine secre- mia is due to decreased insulin secretion and
tion [59]. action [3]. Beta cell function may be disrupted
via increased influx of cholesterol due to inhi-
Management bition of HMG-CoA intracellularly, which leads
to mitochondrial oxidative stress and beta cell
A study by Cooper-DeHoff has demonstrated apoptosis [66]. Insulin resistance via inflamma-
that new-onset diabetes caused by hydrochlo- tion has also been postulated as another mecha-
rothiazide may occur at 9–18 weeks of initiation nism [66]. Under the conditions of obesity and
[60]. On the basis of this finding, we suggest dysregulated metabolic states, statins may acti-
screening for diabetes between 3 and 6 months vate inflammation leading to insulin resistance
after initiation of diuretics, depending on clini- [67]. Another observational study revealed that
cal suspicion. Since hypokalemia is postulated statin use allowed patients to be more liberal in
to be the main trigger for decreased insulin caloric and fat intake leading to increased weight
secretion, maintaining normal potassium levels gain and worsening insulin resistance [68].
Diabetes Ther (2024) 15:2001–2025 2009

Management ratio 1.14, 95% CI 1.06–1.23) [74]. Specifically, the

fluoroquinolone gatifloxacin was shown to have
A recently published study showed that serum an adjusted odds ratio of 16.7 (95% CI 10.4–26.8)
glucose changes within an individual are quite for hyperglycemia [75]. Levofloxacin has also
small, and the benefit of measuring A1c or serum been implicated in hyperglycemia [76]. Another
glucose levels routinely after initiation of a statin study by Mikkelsen et al. showed that although
is likely negligible [69]. However, routine screen- no specific group of antibiotics was associated
ing for diabetes in those that were previously with diabetes risk, there was a slightly higher odds
not diagnosed should be continued according to ratio with narrow-spectrum antibiotics [77]. How-
local guidelines. The incidence of new-onset dia- ever, the authors also concluded that their find-
betes mellitus is noted to be higher with rosuv- ings may simply reflect an increased demand for
astatin compared to atorvastatin (9.5% vs. 7.7%; antibiotics due to the increased risk of infection in
OR 1.25, 95% CI 1.02–1.53; p = 0.03) [70]. Less patients with diabetes. Data from Ye et al. showed
potent statins such as pravastatin are consider- no association between antibiotic use and risk of
ably less diabetogenic [71], so consideration of diabetes, suggesting some potentially confound-
switching statins could be an option. Another ing factors in prior studies [78].
study compared the effects of atorvastatin, pita-
vastatin, and pravastatin on blood glucose and Mechanism of Action
A1c in patients with pre-existing diabetes and
found that pitavastatin and pravastatin had Antibiotic use alters normal gut flora. Animal
minimal effects on both parameters [72]. How- studies have shown that altered gut microbiota
ever, it is highly recommended to assess the ben- increases insulin resistance; furthermore, patients
efits of cardiovascular risk reduction versus any with T2DM or prediabetes have altered gut flora
potential risk of worsening blood sugars before with resultant changes in the balance of short
switching to lower potency statins. Monitoring chain fatty acids [74]. As with other medications,
of lipid panels to assess LDL levels is important causality is often not definitive as the occurrence
in this regard. Reducing the dose of the statin of infections, for which antibiotics are used, can
may also be helpful, in addition to standard dia- itself lead to increased predisposition to develop-
betes medications [3]. It is also worth mention- ment of diabetes by multiple mechanisms includ-
ing niacin use, which has also been linked to ing increased inflammation, hepatic gluconeo-
a moderate increased risk of diabetes develop- genesis, and insulin resistance.
ment regardless of the use of statin; however,
niacin use is now greatly reduced given lack of Management
cardiovascular benefit when added to statin use,
in addition to its increased side effects [73]. There are limited guidelines on treating antibi-
otic-induced hyperglycemia [76]. There is some
dose association with the risk of hyperglycemia
[77]; as such, using the lowest dose for the short-
est duration can mitigate the risk, and avoiding
ANTI‑INFECTIVES
gatifloxacin is reasonable.
Antibiotics
Antivirals
Current Evidence
Current Evidence
A large retrospective study reported that antibi-
otic use for greater than 90 days had a higher risk Protease inhibitors (PI) such as atazanavir or rito-
of diabetes with an adjusted hazard ratio of 1.16 navir are usually part of a combination of drugs
(95% CI 1.07–1.26), and those who used five or that is used to treat human immunodeficiency
more classes were at higher risk (adjusted hazard virus (HIV), and while there has been significant
2010 Diabetes Ther (2024) 15:2001–2025

improvement in morbidity and mortality, side including renal, breast, or neuroendocrine

effects such as increased glucose and lipid levels tumors, by inhibiting tumor proliferation and
have been observed. Hyperglycemia is seen in angiogenesis. A meta-analysis conducted by Lew
3–17% of patients treated with protease inhibitors and Chamberlain showed a 5.3% incidence rate
[76]. Tsiodras et al. showed that protease inhibi- of severe hyperglycemia (> 13.0 mmol/L) [85].
tors had a fivefold increase in the incidence of Clinical trials also show rates of hyperglycemia
hyperglycemia [79]. In addition, NRTIs (nucleo- and new onset of diabetes ranging from 13% to
side reverse transcriptase inhibitors) can also 50% [86]. In the RADIANT-3 trial, the frequency
affect glucose metabolism by causing mitochon- of hyperglycemia was 13% vs. 4% in placebo
drial dysfunction [80]. [87]. In another trial, hyperglycemia occurred
in 14% of patients on temsirolimus [88].
Mechanism of Action
Mechanism
Koster et al. suggest that PIs cause hyperglyce-
mia by inhibiting GLUT4 transporters leading The mTOR pathway regulates glucose metabo-
to insulin resistance, and they can also directly lism by working downstream of insulin bind-
impair insulin secretion in animal models [81]. ing, which ultimately leads to decreased gly-
Carr et al. also report that PIs impair chylomi- cogen synthesis and glucose uptake in skeletal
cron uptake in the liver as well as triglyceride muscle [89]. Decreased insulin secretion is also
clearance resulting in central fat deposition and observed in in vitro studies due to increased beta
insulin resistance [82]. cell apoptosis [90].

Management
Management
Metformin has been postulated to help pre-
Screening with baseline fasting serum glucose vent and to treat everolimus-associated hyper-
followed by monitoring every 3 months for the glycemia as it may affect mTORC1 signalling
first year has been suggested to prevent acute [91]. Busaidy et al. also propose modification
and chronic complications of hyperglycemia of mTOR inhibitor dose if standard treatment
[83]. Metformin should be considered first line of hyperglycemia is not sufficient [92]. Fasting
for pharmacologic management, and there is serum glucose should be measured every 2 weeks
some evidence with pioglitazone use as well, for 1 month after initiation of mTOR inhibitor
but this must be balanced with the risk of fluid therapy, followed by monthly fasting blood
retention and fracture risk [84]. Given the sig- glucose, and A1c levels every 3 months [93]. As
nificant reduction in morbidity and mortality of always, lifestyle changes and patient education
HIV treatment, standard treatment of diabetes are crucial, along with standard antidiabetic
instead of altering doses of PI therapy is typical. agent use.

Tyrosine Kinase Inhibitors (TKIs)

ANTINEOPLASTIC MEDICATIONS Current Evidence

Mammalian Target of Rapamycin (mTOR) TKIs are used to treat a variety of malignancies
Inhibitors such as chronic myeloid leukemia and lung
cancers. It is estimated that hyperglycemia
Current Evidence occurs in 20–36% of patients on nilotinib and
imatinib [94]. Specifically, insulin-like growth
mTOR inhibitors such as everolimus or siroli- factor 1 (IGF-1) receptor TKIs have been reported
mus are used to treat a variety of malignancies, to cause high-grade-severity hyperglycemia in
Diabetes Ther (2024) 15:2001–2025 2011

13–46% of patients, and epidermal growth fac- AKT inhibitors also have low rates of hypergly-
tor receptor (EGFR) TKIs have been reported to cemia, occurring in < 3% for afuresertib [101].
cause hyperglycemia in between 5% and 25% of However, Liu et al. reported that hyperglycemia
patients [95]. is amongst the most common side effects of
PI3K and AKIT inhibitors, occurring up to 80%
Mechanism in trials [102].

Janssen et al. found that nilotinib therapy Mechanism

decreases peripheral insulin sensitivity with
resultant hyperinsulinemia as compensation, PI3K and AKT are downstream mediators of
leading to hyperglycemia [96]. There is also insulin binding and lead to production of gly-
suggestion that TKIs may cause regression of cogen and a decrease in glycolysis [95]. As such,
pancreatic islets, decreased glucose uptake, and when these pathways are disrupted, the intracel-
changes in IGF-1 signalling [97]. lular response to insulin is disturbed, and hyper-
glycemia can occur.
Management
Management
Preventing symptoms of hyperglycemia and
acute complications such as infection, diabetic Metformin is recommended as first-line treat-
ketoacidosis (DKA), and osmotic diuresis while ment, followed by use of an SGLT2 inhibitor,
balancing quality of life would be the goals of which has been found to have greatest reduction
therapy in this cancer specific population, espe- in serum glucose, but carries the risk of eugly-
cially if disease is advanced [98]. Liberalizing cemic DKA [102]. Hyperglycemia may also be
glucose targets (e.g., A1c < 8%) can be considered mitigated by dose interruption or modification
as well. Given that there is an increase in insulin of PI3K and AKT inhibitors as well, in addition
resistance, reasonable first-line options would be to using insulin or sulfonylureas [102].
insulin-sensitizing agents such as metformin.
DPP4 inhibitors are also a good option given Immune Checkpoint Inhibitor (ICI) Therapy
low risk of hypoglycemia. Newer agents such as
SGLT2 inhibitors may have concerns for eugly- Current Evidence
cemia DKA, and sulfonylureas may not be ideal
given unpredictable oral intake in patients who Mulla et al. suggested that use of ICI therapy
may be in advanced stages of cancer. Glucagon- is associated with hyperglycemia in 8.6% of
like peptide 1 receptor agonists (GLP-1 RAs) may patients without pre-existing diabetes [103]. Fur-
lead to weight loss and appetite suppression, thermore, combination checkpoint therapy has
which may not be desired. Thus, insulin ther- higher rates in a meta-analysis [104]. Another
apy may be the best option if hyperglycemia is study reported a significant increase in hyper-
uncontrolled owing to flexibility of dosing [98]. glycemia (27%) after treatment with checkpoint
inhibitors [105].
Phosphoinositide 3‑Kinase (PI3K) and
Protein Kinase B (AKT) Inhibitors Mechanism

Current Evidence ICI therapy has a higher association with type 1

diabetes mellitus (T1DM) physiology due to
These agents are mainly used to treat breast can- immune-mediated damage to pancreatic beta
cer or hematologic malignancies. PI3K inhibi- cells; however, the incidence is reported at
tors may cause hyperglycemia but fortunately 1–2% [103, 106]. Glucocorticoid therapy to
it is quite infrequent, with < 8% affected in help treat other immune-mediated side effects
patients on pilaralisib and pictilisib [99, 100]. of checkpoint inhibitors may further confound
2012 Diabetes Ther (2024) 15:2001–2025

the picture. The mechanism is similar to T1DM, Management

and in the patients that did develop new-onset
diabetes requiring insulin, 83% had low or unde- Implementation of early monitoring and ensur-
tectable C-peptide, and autoantibodies were ing to adjust for renal function when consid-
elevated in 71% [106]. Different classes of ICI ering antidiabetes medication is important.
also seem to cause varying degrees of hypergly- Insulin is usually the mainstay of manage-
cemia. New-onset diabetes occurred most fre- ment, and it is important to ensure that oral
quently with pembrolizumab (2.2%) compared antihyperglycemic agents do not interfere with
to nivolumab (1%), both of which are anti- absorption of immunosuppressants (e.g., GLP-1
programmed cell death 1 (PD-1) antibodies, but RAs may reduce gastrointestinal transit and
0% with ipilimumab, which is an anti-cytotoxic decrease absorption) [112]. Current evidence
T lymphocyte-associated antigen 4 (CTL4-A) based on Munoz Pena et al.’s comprehensive
antibody [106]. review reveals that non-insulin antihyperglyce-
mic medications (e.g., metformin, DPP4 inhibi-
Management tors, SGLT2 inhibitors, GLP-1 RAs) can also be
used that further add cardiovascular and renal
Routine screening with C-peptide, A1c, and benefits without any significant disruptions in
ketones to prevent rapid metabolic decompen- renal or allograft function and immunosuppres-
sation is suggested with endocrinology involve- sive agent doses [112].
ment as needed [107]. Given the mechanism of
action, insulin management is usually required;
glucocorticoid treatment is not recommended to HORMONES
treat ICI-induced diabetes because of exacerba-
tion of hyperglycemia [107]. Somatostatin Analogues (SSAs)

Current Evidence
IMMUNOSUPPRESSIVE AGENTS
SSAs are used to treat acromegaly, Cushing’s dis-
Calcineurin Inhibitors (CNIs) ease, and neuroendocrine tumors. Hyperglyce-
mia has been documented as a common side
Current Evidence effect of SSA use, with 41.4% of patients devel-
oping elevated blood glucose levels in one study
These medications are used for inflammatory [113], and incident diabetes of 19% in another
disorders or immunosuppression after organ study [114]. Specifically, pasireotide tripled the
transplantation, and new-onset diabetes is incidence of hyperglycemia and diabetes in 30%
reported to occur in 15–30% of this patient of patients compared to octreotide and lanreo-
population [108]. A meta-analysis by Heisel et al. tide [115]. However, other studies contradict this
found that the incidence of diabetes in patients finding; Ni et al. used the Surveillance, Epide-
receiving calcineurin inhibitors (tacrolimus, miology and End Results (SEER) database and
cyclosporine) is 13.4% [109]. found a non-statistically significant hazard ratio
(1.19, 95% CI 0.95–1.49) of developing diabe-
tes with SSA use [116]. Interestingly, SSAs have
Mechanism also been used to treat some forms of hyperin-
sulinemic hypoglycemia [117]. There is further
Calcineurin promotes islet beta cell expansion, conflicting evidence regarding development of
and so CNIs lead to pancreatic beta cell apopto- diabetes with SSA use [118, 119], but in general,
sis and decreased insulin secretion [110]. Cyclo- there is enough evidence to warrant monitoring
sporine and tacrolimus have been implicated to of blood sugars.
cause higher rates of hyperglycemia compared
to sirolimus [111].
Diabetes Ther (2024) 15:2001–2025 2013

Mechanism also show that there is a relationship between

low testosterone and hepatic steatosis which
The mechanism of SSA-induced hyperglycemia decreases fatty acid oxidation leading to increase
is complex. SSA therapy is meant to reduce IGF-1 de novo lipid synthesis [125]. Aside from periph-
and growth hormone levels, which should lead eral actions, testosterone may act centrally to
to improved insulin sensitivity. However, SSAs control energy homeostasis and total energy
also act on alpha and beta cells in the pancreas, expenditure [126].
which impairs both glucagon and insulin secre-
tion leading to abnormal regulation of glucose Management
[120]. Some studies have found that SSAs have
beneficial effects on carbohydrate metabolism There is limited literature on the treatment of
as well [121]. hyperglycemia secondary to ADT use. As such,
general measures such as education, lifestyle
Management changes, and standard diabetes medications
should apply [3].
The discontinuation of SSAs leads to reversal
of diabetes [121]. However, in those requiring
long-term use of SSAs, Samson et al. reported
metformin is a good first-line medication fol- OTHER MEDICATIONS
lowed by use of GLP-1 RAs [118]. Active surveil-
lance and standard diabetes treatment includ- Interferon Alpha
ing lifestyle and other antidiabetes medications
also apply [3]; however, it should be noted that This medication is indicated in treatment of
acromegaly and Cushing’s syndrome also have hepatitis C and has been associated with beta
diabetogenic effects. cell destruction and subsequent risk of devel-
oping T1DM by 0.09–0.45% [127]. At times,
DKA has been observed and requires ongoing
Androgen Deprivation Therapy (ADT) insulin management [127]. Insulin resistance
has also been reported in interferon alpha use
Current Evidence [128]. General management measures apply,
with surveillance, and standard antidiabetes
ADT is used for treatment of prostate cancer, medications.
and it has been linked to a 28% risk of diabetes,
with 20% of patients having an A1c increase by Thyroid Hormone Supplementation
1% [122]. In the meta-analysis by Wang et al. of
almost 66,000 patients, ADT use was associated There is evidence that a hyperthyroid state may
with a 39% higher rate of diabetes than non- worsen pre-existing diabetes mellitus, and that
ADT users; there was also a strong association insulin resistance can be improved by restoring
with longer duration of use (> 6 months) [123]. a euthyroid state [129]. It is postulated that a
hyperthyroid state increases glucose absorption,
Mechanism food intake, hepatic gluconeogenesis, and serum
insulin levels, and there is also a complex inter-
Lower testosterone levels increase insulin resist- play of thyroid hormone and its interaction with
ance via several mechanisms. Androgens pre- leptin, ghrelin, and adiponectin that may cause
vent visceral fat accumulation which is known disturbances in non-euthyroid states [130]. Fur-
to increase insulin resistance. Serum adiponec- thermore, the half-life of insulin is decreased in
tin is elevated in hypogonadal men; thus, the a hyperthyroid state as a result of increased deg-
suppression of adiponectin by testosterone may radation [130]. As such, overtreatment of hypo-
lead to decreased adipocytes, improved adipose thyroidism with thyroid hormone replacement
function and sensitivity [124]. Rodent studies may worsen pre-existing diabetes. Metformin
2014 Diabetes Ther (2024) 15:2001–2025

is reported to have beneficial effects on both Mechanism

T2DM and thyroid disease, whereas the use of
sulfonylureas and thiazolidinediones increase Teprotumumab is a monoclonal antibody that
the risk of hyperthyroidism and decreases FT4, inhibits the IGF-1R, which has partial homology
respectively [131]. to the insulin receptor [136]. Thus, hyperglyce-
mia is driven by inhibition of the insulin recep-
Diazoxide tor by teprotumumab [136].

This medication is used to treat hypoglycemia Management

in hyperinsulinemic causes and acts by decreas-
ing insulin secretion and increasing epinephrine There are currently no published guidelines for
secretion, and possibly also by directly increas- teprotumumab-induced hyperglycemia. How-
ing gluconeogenesis and inhibiting peripheral ever, Amarikwa et al. recommend that prior
glucose uptake [132]. Cases of DKA and hyperos- to initiation with teprotumumab, the patient
molar hyperglycemic state (HHS) have also been should be educated regarding the risks of hyper-
reported [2]. There are no guidelines on manage- glycemia, and it is suggested that the patient is
ment; as such, discontinuation of diazoxide if screened for diabetes or prediabetes with an A1c
hyperglycemia occurs is reasonable. and fasting glucose level [137]. In those diag-
nosed with diabetes, optimization of A1c should
Phenytoin be targeted to be < 7% prior to treatment. Since
most hyperglycemia occurs within 12 weeks of
Used as an anti-seizure medication, phenytoin treatment, a repeat A1c should be done during
has been documented to induce hyperglycemia this timeframe. Referral and co-management
via inhibiting insulin release and possibly also with endocrinology and ophthalmology is rec-
due to insulin resistance [133]. Management ommended as well [137].
includes lowering phenytoin dose [133]. A case
report of DKA in a patient with pre-existing dia-
betes also reveals that discontinuation of pheny-
toin resolved the hyperglycemia [134].
UPCOMING ANTINEOPLASTIC
MEDICATIONS
Alpelisib
TEPROTUMUMAB
Alpelisib is a PI3K inhibitor used to treat meta-
Current Evidence
static breast cancer. The mechanism of action is
the same as per the discussion of PI3K inhibitors
Teprotumumab is a new medication used to
above. Shen et al. found that 29% of patients
treat Graves’ orbitopathy and targets the IGF-1
developed grade 3–4 hyperglycemia [138].
receptor. In 2021, Kahaly et al. reported an 8%
Another study reported grade 3 hyperglycemia
incidence rate of hyperglycemia in those using
occurring in 32.7% of patients with median
teprotumumab compared to placebo, and the
onset of 15 days [139]. The grades of hyperglyce-
majority of patients (63%) had pre-existing dia-
mia are classified according to the Common Ter-
betes [135]. A case of HHS has also been reported
minology Criteria for Adverse events (CTCAE):
after the initial infusion of teprotumumab [136].
grade 1 is defined as abnormal glucose above
A more recent observational study reported in
baseline with no medical intervention; grade 2
2023 by Amarikwa et al. found an overall A1c
is defined as change in the daily management
increase of 0.5% at 3 months, and 52% of their
from baseline for a patient with diabetes, or the
patients had hyperglycemia; the risk was higher
initiation of oral antihyperglycemic agents, or
in patients with pre-existing diabetes [137].
new workup for diabetes mellitus; grade 3 is
Diabetes Ther (2024) 15:2001–2025 2015

defined as the initiation of insulin therapy or as an adverse event; however, antitumor

where hospitalization is indicated; grade 4 is response was not significant and there was no
defined as life-threatening consequences requir- further testing of this medication for ongoing
ing urgent intervention; and grade 5 is defined treatment [146].
as death. Optimizing glycemic control prior to
initiation of alpelisib, if possible, should be con- BEZ235
sidered [138]. Initiation of metformin in patients
who developed hyperglycemia was most com- BEZ235 is a combination PI3K and mTOR inhibi-
mon, and 20% required referral to endocrinol- tor for treatment of advanced solid tumors, and
ogy [138]. The importance of early recognition 24% of patients were reported to experience any
and treatment of side effects with dose modifi- grade hyperglycemia [147]. Currently, this agent
cations of alpelisib helped reduce toxicities and is not tolerable for patients because of multiple
can lead to reductions in treatment discontinua- reported adverse effects and the phase I study in
tions which ultimately can improve progression- 2016 was terminated as a result of lack of clinical
free survival [139]. efficacy as well [148].

R1507 GDC‑0980 (Apitolisib)

R1507 is a monoclonal antibody against IGF-1 Apitolisib is a dual PI3K-mTOR inhibitor and
receptor and was studied for the treatment of was used in patients with endometrial cancer.
Ewing’s sarcoma. Use of this medication had Makker et al. reported grade 3 and 4 hypergly-
a low incidence of subclinical hyperglycemia cemia in 46% of patients, and 61% of patients
[140], and in another study by Pappo et al., with pre-existing diabetes had to discontinue
hyperglycemia occurred in < 5% of patients use because of hyperglycemia, with 31% of
[141]. Routine monitoring is suggested. patients with DM requiring dose reductions
[149]. Dolly et al. reported similar findings,
GSK2141795 (Uprosertib) with grade 3 hyperglycemia occurring in 18%
of patients [150].
Uprosertib is an AKT inhibitor used in advanced
solid tumors. Hyperglycemia occurred in 15% of PF‑04691502
patients [142]. A more recent publication found
that combining uprosertib with other agents PF-04691502 is also a dual PI3K inhibitor with
to treat endometrial cancer or melanoma was a reported 27% incidence of hyperglycemia in
poorly tolerated by patients and did not reach treatment of patients with solid tumors [151];
effective doses due to side effects [143]. Hyper- however, no objective antitumor responses were
glycemia was reported in up to 21% of patients observed. Britten et al. found that in patients
[95]. However, a more recent study showed that treated with this agent, there were increases in
combination of uprosertib and another agent fasting serum glucose, insulin, and C-peptide
was poorly tolerated with minimal clinical activ- levels.
ity, but hyperglycemia was not listed as a com-
mon side effect [144].
PF‑05212384/PKI‑587 (Gedatolisib)

MK‑2206
Gedatolisib is a dual PI3K/mTOR inhibitor and is
used in patients with advanced cancer. Shapiro
MK-2206 is used for advanced solid tumors. Yap et al. reported hyperglycemia occurring in 26%
et al. reported that hyperglycemia was mild and of patients treated with this agent [152]. Cur-
transient, but that elevated blood glucose was rently, different combinations of this drug are
still seen in 57% of patients [145]. Ramanathan being investigated for breast cancer, colorectal
et al. reported a 30% incidence of hyperglycemia
2016 Diabetes Ther (2024) 15:2001–2025

cancer, and acute myeloid leukemia in ongoing situation. Metformin has generally been first-
clinical trials. line treatment in all the above causes of medica-
tion-induced hyperglycemia given its safety and
General Management Principles of efficacy. GLP-1 RAs and glucose-dependent insu-
Medication‑Induced Hyperglycemia linotropic polypeptide (GIP) receptor/GLP-1RAs
were initially designed for management of dia-
Overall, the potential of a drug to cause hyper- betes; however, it is now well known that these
glycemia and diabetes needs to be known and agents can also lead to significant weight loss,
balanced with the patient’s underlying risk fac- with side effects including nausea and abdomi-
tors. More importantly, the benefits and risks of nal pain. While the weight loss may be desired
continuing the current medication, the duration in patients who have overweight/obesity, these
and dose of the medication, and a discussion should be avoided in patients where weight loss
with the patient regarding future microvascular is unwanted, such as patients with advanced
and macrovascular complications should be had, cancer or in those that are frail or malnourished.
especially if the patient has pre-existing comor- In addition, the nausea and vomiting may also
bidities such as cardiovascular or renal disease. affect absorption of crucial medications (e.g.,
The current landscape of evidence leaves some immunosuppression for organ transplant, oral
questions unanswered, including the precise role antineoplastic agents) and should be reconsid-
of the dose and exposure time of each medica- ered. SGLT2 inhibitors are another class of medi-
tion, and these would be excellent future direc- cations that may be used for glycemic control,
tions of research. but there is a risk of euglycemic DKA especially
Instituting measures to assess glycemic status in sick individuals [153]. Sulfonylureas in gen-
prior to initiation of a diabetogenic medication eral should be avoided in those who have unpre-
and ongoing monitoring during treatment is dictable oral intake because of the risk of hypo-
critical, as most medications are duration and glycemia; DPP4 inhibitors have minimal risk of
dose dependent. The advent of technology with hypoglycemia but are not as potent [98].
continuous glucose monitors can also be imple-
mented for convenience and real-time monitor-
ing to target specific periods of hyperglycemia
(e.g., fasting vs. postprandial). The involvement CONCLUSION
of allied health including dieticians, diabetes
nurse educators, and referrals or consultations Medication-induced hyperglycemia requires
with endocrinology can also be of use. Educa- recognition, screening, monitoring, and proper
tion of patients regarding acute symptoms of management to prevent acute and chronic com-
hyperglycemia, including polyuria, polydipsia, plications. Specifically, the growing prevalence
or weight loss, is also essential. and incidence of diabetes globally, the increas-
In general, treatment of medication-induced ing number of antineoplastic agents and their
hyperglycemia and diabetes is similar to stand- prolonged use, and the large number of patients
ard treatment with lifestyle measures including with pre-existing cardiovascular disease that
balanced diet and exercise applying to almost may be exacerbated by hyperglycemia and dia-
all cases. Acute episodes of hyperglycemia, par- betes with the aforementioned antihypertensive
ticularly those causing DKA or HHS, should be medications warrant special attention and ongo-
treated with IV insulin. The medications listed ing vigilance for medication-induced hypergly-
above that cause pancreatic beta cell destruc- cemia by all health care professionals.
tion, such as immune checkpoint inhibitors or
interferon alpha, may require upfront treatment Author Contribution. Akshay B. Jain was
with insulin. The wide array of non-insulin involved in conceptualizing, literature review,
antidiabetic medications should also be selec- writing, editing, and creation of the tables and
tively used on the basis of each patient’s specific figure. Valerie Lai was involved in literature
Diabetes Ther (2024) 15:2001–2025 2017

review, writing, editing, and creation of the not permitted by statutory regulation or exceeds
tables and figure. the permitted use, you will need to obtain per-
mission directly from the copyright holder. To
Funding. No funding or sponsorship was view a copy of this licence, visit http://c​ reati​ veco​
received for this study or publication of this mmons.​org/​licen​ses/​by-​nc/4.​0/.
article.

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