What oral anti-hyperglycemic should I use to replace Sodium-Glucose Linked Transporter 2 inhibitors (SGLT2i)?

From the Guidelines

Metformin is the most appropriate oral anti-hyperglycemic to replace SGLT2 inhibitors, given its high efficacy, low cost, and minimal hypoglycemia risk when used as monotherapy. This recommendation is based on the American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) consensus report, which states that metformin remains the first-line medication for management of type 2 diabetes due to its high efficacy in lowering HbA1c, good safety profile, and low cost 1.

When considering alternative options, it's essential to weigh the benefits and risks of each medication. GLP-1 receptor agonists, such as semaglutide or dulaglutide, offer cardiovascular benefits and weight loss similar to SGLT2 inhibitors but require injection. DPP-4 inhibitors, like sitagliptin 100mg daily, are weight-neutral with low hypoglycemia risk and have been shown to have a similar effect on HbA1c levels compared to other agents, except for a slight increase in HbA1c level compared to sulfonylureas and thiazolidinediones 1. Sulfonylureas, such as glimepiride 1-8mg daily, effectively lower blood glucose but carry a higher risk of hypoglycemia. Thiazolidinediones, like pioglitazone 15-45mg daily, help with insulin resistance but may cause fluid retention.

Key factors to consider when selecting an alternative to SGLT2 inhibitors include:

• Cardiovascular risk: GLP-1 receptor agonists and SGLT2 inhibitors have demonstrated cardiovascular benefits.
• Kidney function: Metformin and DPP-4 inhibitors are generally safe in patients with kidney disease, but SGLT2 inhibitors require careful monitoring of renal function.
• Weight management goals: GLP-1 receptor agonists and SGLT2 inhibitors promote weight loss, while thiazolidinediones may cause weight gain.
• Hypoglycemia risk: DPP-4 inhibitors and metformin have a lower risk of hypoglycemia compared to sulfonylureas.

Ultimately, the choice of oral anti-hyperglycemic medication should be guided by individual patient needs and characteristics, and consultation with a healthcare provider is essential to determine the most appropriate alternative to SGLT2 inhibitors.

From the Research

Alternatives to SGLT2i

When considering an alternative to Sodium-Glucose Linked Transporter 2 inhibitors (SGLT2i) for the treatment of type 2 diabetes, several oral anti-hyperglycemic options are available. The choice of replacement therapy depends on various factors including the patient's medical history, current health status, and the specific reasons for discontinuing SGLT2i.

Metformin as a First-Line Option

• Metformin is widely recommended as a first-line therapy for patients with type 2 diabetes due to its efficacy in reducing mortality and cardiovascular morbidity, as well as its acceptable adverse effect profile 2, 3.
• It is generally well-tolerated, with common adverse effects including gastrointestinal disorders and rare cases of lactic acidosis, particularly in patients with renal impairment.
• The harm-benefit balance of metformin monotherapy remains favorable in most patients with type 2 diabetes when dietary measures alone are not sufficient 2.

DPP-4 Inhibitors as an Alternative

• Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is another option for the treatment of type 2 diabetes, offering effective glycemic control with a low risk of hypoglycemia and a neutral effect on body weight 4, 5.
• Sitagliptin has been shown to be well-tolerated and effective in various patient populations, including those with renal impairment and established cardiovascular disease.
• The TECOS CV safety trial demonstrated that sitagliptin was noninferior to placebo in terms of the risk of major adverse cardiac events in patients with type 2 diabetes and established cardiovascular disease 4.

Network Meta-Analysis of Oral Hypoglycemic Drugs

• A network meta-analysis of randomized controlled trials compared the efficacy of 11 major oral hypoglycemic drugs, including metformin, repaglinide, and gliclazide, in treating type 2 diabetes 6.
• The analysis found that repaglinide, gliclazide, and metformin were among the top three anti-diabetics in terms of reducing glycosylated hemoglobin and fasting plasma glucose levels.
• There was no significant difference in efficacy between metformin and repaglinide, suggesting that both could be considered as first-line options for the treatment of type 2 diabetes 6.

Considerations for Replacement Therapy

• When replacing SGLT2i, it is essential to consider the individual patient's characteristics, medical history, and the reasons for discontinuing SGLT2i.
• The choice of replacement therapy should be based on the patient's specific needs and the potential benefits and risks associated with each alternative option.
• Healthcare providers should carefully evaluate the available evidence and consider factors such as efficacy, safety, and cost when selecting an alternative oral anti-hyperglycemic agent 3.