Review
Copyright ©The Author(s) 2021.
World J Diabetes. Jul 15, 2021; 12(7): 1010-1025
Published online Jul 15, 2021. doi: 10.4239/wjd.v12.i7.1010
Table 1 Summary of reported characteristics of hyperglycemia incidence, onset and severity with the use of current chemotherapy agents
Characteristics by drug class
Glucocorticoids
5-FU and analogs
PI3K/mTor inhibitors
Immune checkpoint inhibitors
Incidence of new or worsening hyperglycemia Significant, 34%-94%Common, 11.6% DM, 11.3% IFGSignificant, 12%-50%Rare, 0.2%-4.9%
Onset of hyperglycemia after first use Acutely Majority by 3 mo; 3/4 early (3rd cycle); 1/4 up to 1 yr laterMajority after first useMajority by 4 mo, can be after first use, can be up to 1 yr later
Severity of hyperglycemic events Usually mild, Severe possible, Multiple reports of DKA and some HHSMild, Case reports of DKAMild, No DKAModerate to severe, 77.8% DKA
Table 2 Hyperglycemia can be a class or drug-specific effect and may not be reversible with discontinuation
Characteristics by drug class
Glucocorticoids
5-FU and analogs
PI3K/mTOR inhibitors
Immune checkpoint inhibitors
Class effect on hyperglycemiaYesYesYesNegligible risk with the CTLA-4 inhibitor, ipililmumab
Does occur with all PD-1 and PD-L1 inhibitors, most significantly when combined
Reversibility of hyperglycemiaYesNoYesNo
Table 3 The underlying mechanisms and treatment considerations of hyperglycemia differ between chemotherapy classes

Etiology of hyperglycemia
Treatment considerations
GlucocorticoidsMajor: Insulin resistanceOral hypoglycemics possible for mild
Minor: Decreased insulin releaseConsider selecting insulins with duration of action to match that of the steroid being given
5-FU and analogsMajor: Decreased insulin release and productionDiet or oral hypoglycemics for mild
Insulin for severe
PI3K/mTOR inhibitorsMajor: Insulin resistance Diet or metformin for mild
Immune checkpoint inhibitorsMajor: Profound insulin deficiencyImmediate initiation of insulin in new onset hyperglycemia
Switch to insulin in pre-existing T2DM