What medications are recommended for a patient with uncontrolled diabetes and obesity?

From the Guidelines

For patients with uncontrolled diabetes and obesity, the most effective medication regimen typically includes a combination of metformin, GLP-1 receptor agonists such as semaglutide or tirzepatide, and SGLT-2 inhibitors like empagliflozin or dapagliflozin, as these promote weight loss and improve glycemic control while providing cardiovascular and kidney protection. When choosing glucose-lowering medications for people with type 2 diabetes and overweight or obesity, it is recommended to prioritize medications with a beneficial effect on weight, such as GLP-1 receptor agonists and dual GIP and GLP-1 receptor agonists like tirzepatide 1. The preferred pharmacotherapy should be a glucagon-like peptide 1 receptor agonist or dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptor agonist with greater weight loss efficacy, especially considering their added weight-independent benefits 1. Weight management pharmacotherapy should be considered for people with diabetes and overweight or obesity along with lifestyle changes, and the potential benefits and risks must be considered 1. In adults with obesity or overweight with weight-related complications, the use of semaglutide 2.4 mg with lifestyle modifications is suggested compared with lifestyle modifications alone, given its glucoregulatory benefits and approval for the treatment of type 2 diabetes 1. Key considerations in the treatment plan include the patient's specific health profile, kidney function, cardiovascular risk, and insurance coverage, as well as regular monitoring of blood glucose, kidney function, and potential side effects, with lifestyle modifications remaining foundational to any medication regimen 1. It is also important to note that weight management pharmacotherapy indicated for chronic therapy should be continued beyond reaching weight loss goals to maintain the health benefits, as sudden discontinuation often results in weight gain and worsening of cardiometabolic risk factors 1. For those not reaching treatment goals, reevaluation of weight management therapies and intensification of treatment with additional approaches, such as metabolic surgery or structured lifestyle management programs, should be considered 1.

From the FDA Drug Label

At Week 24, initial therapy of JARDIANCE in combination with metformin provided statistically significant reductions in HbA1c (p-value <0. 01) compared to the individual components Treatment with JARDIANCE 10 mg or 25 mg daily provided statistically significant reductions in HbA1c (p-value <0. 0001), FPG, and body weight compared with placebo JARDIANCE 10 mg or 25 mg used in combination with linagliptin 5 mg provided statistically significant improvement in HbA1c (p-value <0.0001) and FPG (p-value <0. 001) compared to the individual components Treatment with JARDIANCE/linagliptin 25 mg/5 mg or JARDIANCE/linagliptin 10 mg/5 mg daily also resulted in a statistically significant reduction in body weight compared to linagliptin 5 mg (p-value <0. 0001)

Medications recommended for a patient with uncontrolled diabetes and obesity:

• Empagliflozin (JARDIANCE): can be used as initial therapy in combination with metformin, or as add-on therapy to metformin, sulfonylurea, pioglitazone, or insulin.
• Metformin: can be used in combination with empagliflozin as initial therapy.
• Linagliptin: can be used in combination with empagliflozin as add-on therapy to metformin.
• Pioglitazone: can be used in combination with empagliflozin as add-on therapy.
• Insulin: can be used in combination with empagliflozin as add-on therapy.

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From the Research

Medications for Uncontrolled Diabetes and Obesity

Medications for patients with uncontrolled diabetes and obesity include:

• SGLT2 inhibitors, such as empagliflozin, which have been shown to improve glycemic control, reduce body weight, and lower blood pressure 3, 4, 5, 6
• GLP-1 receptor agonists, such as liraglutide, which have been shown to improve glycemic control, reduce body weight, and lower cardiovascular risk factors 3, 4, 7, 5, 6
• Combination therapy with SGLT2 inhibitors and GLP-1 receptor agonists, which may have additive effects on glycemic control, body weight, and cardiovascular risk factors 3, 4, 7

Benefits of Combination Therapy

The benefits of combination therapy with SGLT2 inhibitors and GLP-1 receptor agonists include:

• Improved glycemic control, with significant reductions in glycated hemoglobin and fasting plasma glucose 3, 4
• Reduced body weight, with significant reductions in body weight and improvements in body mass index 3, 4
• Lower blood pressure, with significant reductions in systolic and diastolic blood pressure 3, 4
• Reduced cardiovascular risk factors, with significant reductions in major cardiovascular events and all-cause mortality 4, 5, 6

Considerations for Treatment

Considerations for treatment with SGLT2 inhibitors and GLP-1 receptor agonists include:

• Estimated glomerular filtration rate, with SGLT2 inhibitors most effective if the estimated glomerular filtration rate is more than 60 ml per min per 1·73m2 at initiation 6
• Risk of diabetic ketoacidosis, with SGLT2 inhibitors contraindicated in patients at high risk of diabetic ketoacidosis 6
• History of medullary thyroid cancer, with GLP-1 receptor agonists contraindicated in patients with a history of medullary thyroid cancer 6
• History of pancreatitis, with GLP-1 receptor agonists used with caution in patients with a history of pancreatitis of a known cause 6