Diabetes Management

Introduction to Medications

The American Diabetes Association recommends various medications for diabetes management, including Prandin (Repaglinide) as a short-acting insulin secretagogue, which may be useful for patients with irregular meal schedules and can be used in patients with renal impairment with appropriate dose adjustment and monitoring, with a higher risk of hypoglycemia similar to sulfonylureas 1

The American Diabetes Association recommends Metformin as the preferred initial agent for most patients with type 2 diabetes, based on evidence from multiple studies 2, 3, 4
DPP-4 inhibitors can be used in combination with metformin, sulfonylureas, thiazolidinediones, and insulin, as stated by the American College of Physicians, and may be considered as add-on to metformin for patients without cardiovascular disease 5

For patients with severe renal impairment, the American Society of Nephrology recommends a dose adjustment, with a maximum of 50 mg daily for eGFR 30-50 mL/min/1.73 m² and a maximum of 25 mg daily for eGFR <30 mL/min/1.73 m² 6
Linagliptin, a DPP-4 inhibitor, provides moderate glycemic control without requiring dose adjustment in patients with renal impairment, making it valuable for patients with kidney disease, as demonstrated in the CAROLINA trial 7
The standard dose of linagliptin is 5 mg once daily, with or without food, and no dose adjustment is required for renal impairment, hepatic impairment, elderly patients, or obese patients 8, 3, 9

The American Heart Association suggests using sitagliptin with caution in patients at risk for heart failure, as other DPP-4 inhibitors have been associated with increased risk of heart failure hospitalization 10
Patients with heart failure or at high risk for heart failure should avoid saxagliptin, and DPP-4 inhibitors, especially saxagliptin, while GLP-1 receptor agonists should be avoided in patients with recent heart failure decompensation, as recommended by the American College of Cardiology, the European Society of Cardiology, and the American Heart Association (Class III recommendation, Level B evidence) 10, 11, 12
DPP-4 inhibitors do not reduce cardiovascular events, unlike SGLT2 inhibitors and GLP-1 receptor agonists, as stated by the European Society of Cardiology 11, 12
SGLT2 inhibitors probably reduce progression to CKD compared to DPP-4 inhibitors (RR 0.62) 13

The American Gastroenterological Association recommends using sitagliptin with caution in patients with a history of pancreatitis, as cases of pancreatitis have been reported in clinical trials 6
Patients with a history of pancreatitis, gastroparesis, MEN2, or medullary thyroid cancer should avoid GLP-1 receptor agonists 14
The American College of Obstetricians and Gynecologists recommends that sitagliptin not be used in women who are pregnant or actively trying to conceive, and also not recommended for use in women who are nursing 15
The American College of Obstetricians and Gynecologists suggests that women of reproductive potential should receive counseling regarding reliable contraception methods 15

Metformin is recommended as the preferred first-line agent for patients with normal renal function by the European Society of Cardiology and the American Diabetes Association 5, 16
For patients with established cardiovascular disease or at high cardiovascular risk, SGLT2 inhibitors or GLP-1 receptor agonists are preferred over DPP-4 inhibitors as second-line therapy by the American Diabetes Association and European Heart Society 11, 12, 16
The median monthly costs for maximum approved daily doses of DPP-4 inhibitors are:
Medication AWP NADAC
Saxagliptin (5 mg) $490 $392
Alogliptin (25 mg) $234 $170

Medication	AWP	NADAC
Saxagliptin (5 mg)	$490	$392
Alogliptin (25 mg)	$234	$170

DPP-4 inhibitors have a low risk of hypoglycemia when used as monotherapy, are weight neutral or associated with minimal weight changes, and do not increase the risk of cardiovascular disease for sitagliptin, saxagliptin, and alogliptin, although saxagliptin has been associated with increased risk of heart failure hospitalization in the SAVOR-TIMI 53 trial and alogliptin showed a trend toward increased heart failure hospitalizations in the EXAMINE trial 18, 13, 10, 19
When initiating either class of medication in patients on insulin or sulfonylureas, consider reducing doses of these agents by 20-50% to prevent hypoglycemia 14