What is the best alternative for a 61-year-old male (YOM) with poorly controlled type 2 diabetes mellitus (DM) who was previously on metformin, gliclazide, and sitagliptin (DPP-4 inhibitor) but was switched to Ozempic (semaglutide) and is now experiencing gastrointestinal (GI) side effects?

From the Guidelines

The best alternative for a 61-year-old male with poorly controlled type 2 diabetes experiencing GI side effects from Ozempic (semaglutide) would be to switch back to his previous regimen of metformin, gliclazide, and sitagliptin with dose adjustments, as this combination has a more established safety profile and fewer GI side effects compared to GLP-1 receptor agonists 1.

Considerations for Switching Back to Previous Regimen

• The patient's previous regimen of metformin, gliclazide, and sitagliptin can be resumed with dose adjustments to minimize the risk of hypoglycemia, particularly when combining sulfonylureas with DPP-4 inhibitors 1.
• Metformin has a high glucose-lowering efficacy and a neutral effect on weight, but may require dose adjustment based on renal function 1.
• Gliclazide, a sulfonylurea, has a high glucose-lowering efficacy but carries a risk of hypoglycemia and weight gain 1.
• Sitagliptin, a DPP-4 inhibitor, has intermediate glucose-lowering efficacy, a neutral effect on weight, and minimal risk of hypoglycemia when used as monotherapy 1.

Alternative Options

• If the patient's GI side effects persist, an SGLT-2 inhibitor like empagliflozin (Jardiance) 10 mg daily could be added to his previous regimen instead, considering its cardiovascular and kidney benefits 1.
• Dulaglutide (Trulicity) at a starting dose of 0.75 mg once weekly could be considered as an alternative GLP-1 receptor agonist with potentially fewer GI side effects, but its use should be weighed against the patient's individual risk factors and medical history 1.

Monitoring and Follow-up

• The patient should monitor blood glucose levels regularly during any medication transition and maintain close follow-up with his healthcare provider to ensure adequate glycemic control.
• Proper hydration, smaller meals, and avoiding high-fat foods can help manage GI side effects associated with GLP-1 agonists, which often improve with time, typically within 4-8 weeks of treatment.

From the FDA Drug Label

Saxagliptin has been studied as monotherapy and in combination with metformin HCl, glyburide, and thiazolidinedione (pioglitazone and rosiglitazone) therapy Treatment with saxagliptin 5 mg and 2.5 mg doses produced statistically significant improvements in A1C, fasting plasma glucose (FPG), and 2-hour postprandial glucose (PPG) following a standard oral glucose tolerance test (OGTT), compared to control.

The best alternative for a 61-year-old male with poorly controlled type 2 diabetes mellitus who was previously on metformin, gliclazide, and sitagliptin but was switched to Ozempic and is now experiencing gastrointestinal side effects is to switch back to a DPP-4 inhibitor, such as saxagliptin.

• Saxagliptin has been shown to be effective in improving glycemic control in patients with type 2 diabetes mellitus, including those who are inadequately controlled on metformin alone or in combination with other therapies 2.
• Key benefits of saxagliptin include its ability to improve A1C, FPG, and PPG, with a low risk of hypoglycemia and no significant effect on body weight.

From the Research

Alternative Treatment Options

The patient, a 61-year-old male with poorly controlled type 2 diabetes mellitus (DM), was initially on metformin, gliclazide, and sitagliptin but was switched to Ozempic (semaglutide) due to poor control. However, he is experiencing gastrointestinal (GI) side effects from Ozempic. Considering his history and current situation, the best alternative to switch back to would be a DPP-4 inhibitor, given his previous tolerance to sitagliptin 3.

Rationale for Switching Back to a DPP-4 Inhibitor

• DPP-4 inhibitors, such as sitagliptin, have been shown to be effective, well-tolerated, and safe in the treatment of type 2 diabetes in monotherapy or in combination with metformin or thiazolidinediones with minimal side effects 3.
• The patient was previously on sitagliptin, indicating he could tolerate DPP-4 inhibitors, making it a viable option to return to this class of medication.
• DPP-4 inhibitors can be used in combination with other antidiabetic compounds, including metformin and sulfonylureas, without significant drug-drug interactions, except for the need to potentially reduce the dose of sulfonylureas to avoid hypoglycemia 4.

Considerations for Other Options

• Sodium-glucose cotransporter type 2 inhibitors (SGLT2 inhibitors) could be considered as an alternative, especially in patients with obesity, hypertension, or a history of cardiovascular disease. However, the decision between a DPP-4 inhibitor and an SGLT2 inhibitor should be guided by individual patient characteristics, such as the presence of renal impairment, obesity, or cardiovascular disease 5.
• Combining a DPP-4 inhibitor with an SGLT2 inhibitor is also a viable option for patients with type 2 diabetes, offering complementary glucose-lowering effects without inducing hypoglycemia. Fixed-dose combinations are available and can simplify anti-hyperglycemic therapy and improve drug compliance 6.

Safety and Efficacy of DPP-4 Inhibitors

• DPP-4 inhibitors, including alogliptin, have similar overall clinical efficacy and safety profiles in patients with type 2 diabetes, with the main differences being in potency, target selectivity, and pharmacokinetic properties 7.
• Treatment with DPP-4 inhibitors is expected to produce a mean glycated hemoglobin (HbA1c) decrease of 0.5%-0.8%, with about 40% of diabetic subjects reaching the HbA1c goal <7% 7.