Management of hypoglycemia in older adults with type 2 diabetes

Figures & data

Figure 1. Glycemic thresholds for secretion of counter-regulatory hormones and onset of symptoms in response to hypoglycemia [28]. Republished with permission of John Wiley and Sons, Ltd., from Hypoglycaemia in Clinical Diabetes, Frier & Fisher 1999, permission conveyed through Copyright Clearance Center, Inc.

Table 1. Considerations for glucose-lowering therapy in older adults [21,44,49,50].

Therapy	Expected HbA1c reduction (%) [44]	CV effects – ASCVD	CV effects – CHF	Additional considerations	Considerations for older adults	Monthly cost
Metformin	1–2	Potential benefit	Neutral	Gastrointestinal side effects common Potential B12 deficiency	Recommended initial pharmacotherapy after lifestyle Low risk of hypoglycemia Contraindicated with eGFR <30	Low
SGLT2 inhibitors	0.5–0.7	Benefit: Canagliflozin Empagliflozin*	Benefit: Canagliflozin Empagliflozin	FDA black box: Risk of amputation (canagliflozin) Risk of bone fractures (canagliflozin) Genitourinary infections Volume depletion DKA risk (all agents, rare in T2D) Increased LDL cholesterol Risk of Fournier’s gangrene	Convenient oral route Causes some weight loss Causes slight reduction in BP Canagliflozin: not recommended for eGFR <45 Dapagliflozin: not recommended with eGFR <60; contraindicated with eGFR <30 Empagliflozin: contraindicated with eGFR <30	High
DPP-4 inhibitors	0.5–0.8	Neutral	Potential risk: Saxagliptin Alogliptin	Potential risk of acute pancreatitis Joint pain	Convenient oral route Renal dose adjustment required except for linagliptin; can be used in renal impairment	High
GLP-1 RAs	1–1.5	Neutral: Lixisenatide Exenatide ER Benefit: Liraglutide*	Neutral	FDA black box: risk of thyroid C-cell tumors (liraglutide, abiglutide, dulaglutide, exenatide ER) Gastrointestinal side effects common Acute pancreatitis risk Injection site reactions	Injection route requires good visual acuity and motor skills Weight loss may be undesirable Exenatide: not indicated with eGFR <30 Lixisenatide: caution with eGFR <30 Increased risk of side effect in patients with renal impairment	High
TZDs	1–2	Potential benefit: Pioglitazone	Increased risk	FDA black box: CHF (pioglitazone, rosiglitazone) Benefit in NASH Fluid retention (edema, CHF) Bladder cancer (pioglitazone) Increased LDL cholesterol (rosiglitazone) Risk of bone fractures	Generally not recommended in renal impairment due to potential for fluid retention Use with caution in those at risk for falls/fractures	Low
Sulfonylureas (Second generation)	1–2	Neutral	Neutral	Risk of hypoglycemia FDA Special Warning on increased risk of CV mortality based on studies of an older SU (tolbutamide)	Use with caution Glyburide not recommended Glipizide and glimepiride: initiate conservatively to avoid hypoglycemia	Low
Insulin	1.5–3.5	Neutral	Neutral	Risk of hypoglycemia Weight gain	Injection route requires good visual acuity and motor skills Lower insulin doses required with decrease in eGFR; titrate per clinical experience	Low (human insulin) High (analogs)

*FDA approved for CVD benefit.

ASCVD = atherosclerotic cardiovascular disease; BP = blood pressure; CHF = congestive heart failure; CV = cardiovascular; DKA = diabetic ketoacidosis; DPP-4 = dipeptidyl peptidase-4; eGFR = estimated glomerular filtration rate (mL/min/1.73 m²); ER = extended release; FDA = US Food and Drug Administration; GLP-1 RA = glucagon-like peptide-1 receptor agonist; HbA1c = glycated hemoglobin; LDL = low-density lipoprotein; NASH = non-alcoholic steatohepatitis; SGLT2 = sodium-glucose co-transporter 2; SU = sulfonylurea; T2D = type 2 diabetes; TZD = thiazolidinedione.

Cryer PE. Mechanisms of sympathoadrenal failure and hypoglycemia in diabetes. J Clin Invest. 2006;116:1470–1473.

 PubMed Web of Science ®Google Scholar

American Diabetes Association. Glycemic targets: standards of medical care in diabetes. Diabetes Care. 2018;41:S55–S64.

 PubMed Web of Science ®Google Scholar

Lipska KJ, Krumholz H, Soones T, et al. Polypharmacy in the aging patient: a review of glycemic control in older adults with type 2 diabetes. JAMA. 2016;315:1034–1045.

 PubMed Web of Science ®Google Scholar

American Diabetes Association. 9. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2019. Diabetes Care. 2019;42(Suppl 1):S90–S102.

 PubMed Web of Science ®Google Scholar

Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012;35:1364–1379.

 PubMed Web of Science ®Google Scholar