From the Guidelines
The most effective diabetic medicine to pair with Metformin is an SGLT2 inhibitor, such as Empagliflozin, or a GLP-1 receptor agonist, such as Semaglutide, as they have demonstrated cardiovascular benefits and can improve glucose control through different mechanisms. When considering combination therapy with Metformin, it's essential to take into account the patient's individual characteristics, such as the presence of established atherosclerotic cardiovascular disease (ASCVD) or indicators of high ASCVD risk, heart failure (HF), or chronic kidney disease (CKD) 1. The choice of medication to add to Metformin should be based on the patient's specific needs and preferences, as well as the potential benefits and risks of each medication. Some key factors to consider when selecting a medication to pair with Metformin include:
- Efficacy in reducing HbA1c levels
- Risk of hypoglycemia
- Effects on body weight
- Potential side effects
- Cost
- Patient preferences According to the most recent guidelines, an SGLT2 inhibitor or a GLP-1 receptor agonist with demonstrated cardiovascular benefit is recommended as part of the glucose-lowering plan for individuals with type 2 diabetes and established ASCVD or indicators of high ASCVD risk, HF, or CKD, independent of A1C and metformin use 1. For example, Empagliflozin, an SGLT2 inhibitor, has been shown to reduce the risk of cardiovascular events and improve glucose control when used in combination with Metformin 1. Similarly, Semaglutide, a GLP-1 receptor agonist, has been demonstrated to improve glucose control and reduce the risk of major adverse cardiovascular events when used in combination with Metformin 1. Ultimately, the choice of medication to pair with Metformin will depend on the individual patient's needs and circumstances, and should be made in consultation with a healthcare provider.
From the FDA Drug Label
ACTOS Plus Metformin Studies Two clinical studies were conducted with ACTOS in combination with metformin Both studies included patients with type 2 diabetes on metformin, either alone or in combination with another antidiabetic agent. In the first study, 328 patients were randomized to receive either 30 mg of ACTOS or placebo once daily for 16 weeks in addition to their current metformin regimen When compared to placebo at Week 16, the addition of ACTOS to metformin significantly reduced the mean HbA1c by 0.8% and decreased the mean FPG by 38 mg/dL.
- Pioglitazone (ACTOS) is a diabetic medicine that can be paired well with Metformin.
- The combination of Pioglitazone and Metformin has been shown to significantly reduce HbA1c and FPG levels in patients with type 2 diabetes.
- This combination therapy may be considered for patients who are not adequately controlled on Metformin alone 2.
From the Research
Diabetic Medicines Paired with Metformin
- Dipeptidyl peptidase-4 (DPP-4) inhibitors can be paired with metformin to lower HbA(1c) levels in patients with type 2 diabetes mellitus, with a similar effect to sulfonylureas or pioglitazone 3.
- Sodium glucose cotransporter-2 (SGLT2) inhibitors can be used as add-on therapy to metformin in patients who do not achieve glycemic targets with metformin alone, with a low risk of hypoglycemia 4.
- The combination of DPP-4 inhibitors and metformin provides an additive or synergistic effect on metabolic control in patients with type 2 diabetes mellitus 5.
- Triple combination therapy with a DPP-4 inhibitor, metformin, and sulfonylurea can result in marked improvements in HbA1c levels in patients with type 2 diabetes mellitus 6.
- DPP-4 inhibitors may be considered a clinically stable choice for second-line therapy after completing maximally tolerated doses of metformin, despite sulfonylureas being more efficacious in lowering HbA1c 7.
Comparison of Medicines
- DPP-4 inhibitors have a favourable weight profile compared to sulfonylureas and pioglitazone 3.
- SGLT2 inhibitors have a low risk of hypoglycemia when used in combination with metformin 4.
- Sulfonylureas are considered better than DPP-4 inhibitors for treatment in patients with cardiovascular disease history and hypoglycemia 7.