Commercially Available Combined Diabetes Tablets
Multiple fixed-dose combination tablets containing metformin plus another antidiabetic agent are commercially available in the United States, including metformin combined with sulfonylureas, DPP-4 inhibitors, SGLT2 inhibitors, and thiazolidinediones. 1
Metformin + Sulfonylurea Combinations
- Metformin + glipizide combination tablets are available, combining a biguanide with a second-generation sulfonylurea 1
- Metformin + glyburide combination tablets are available, though glyburide should be avoided in patients with renal impairment 1, 2
- Metformin + glimepiride combination tablets are available as another sulfonylurea option 1
- These combinations carry a 4-fold higher risk for hypoglycemia compared to metformin alone 3
Metformin + DPP-4 Inhibitor Combinations
- Metformin + sitagliptin is available as a fixed-dose combination, with sitagliptin costing approximately $500-657 per month at maximum dose 1, 4
- Metformin + saxagliptin is available as a fixed-dose combination 1
- Metformin + linagliptin is available as a fixed-dose combination 1
- Metformin + alogliptin is available as a fixed-dose combination and is the most affordable DPP-4 inhibitor option at $145-175 per month 1, 4
- DPP-4 inhibitor combinations have low risk of hypoglycemia and are weight-neutral 1
Metformin + SGLT2 Inhibitor Combinations
- Metformin + empagliflozin is available as a fixed-dose combination, with empagliflozin demonstrating cardiovascular mortality benefits in trials 1
- Metformin + dapagliflozin is available as a fixed-dose combination 1
- Metformin + canagliflozin is available as a fixed-dose combination 1, 5
- Metformin + ertugliflozin is available as a fixed-dose combination and is the most affordable SGLT2 inhibitor option at $312-343 per month 1
- SGLT2 inhibitor combinations provide cardiovascular and renal protection with 12-26% risk reduction for atherosclerotic cardiovascular disease 1, 6
SGLT2 Inhibitor + DPP-4 Inhibitor Combinations
- Empagliflozin + linagliptin is available as a fixed-dose combination tablet, demonstrating bioequivalence to individual tablets 7, 8
- Dapagliflozin + saxagliptin is available as a fixed-dose combination tablet 7, 8
- Ertugliflozin + sitagliptin was in development as a fixed-dose combination 7
- These combinations are safe without increased hypoglycemia risk and provide complementary glucose-lowering mechanisms 7, 8
Metformin + Thiazolidinedione Combinations
- Metformin + pioglitazone combination tablets are available 1
- Thiazolidinedione combinations increase risk for congestive heart failure and bone fractures compared to other options 3
- Pioglitazone costs approximately $3-5 per month for generic formulations at maximum dose 1
Clinical Considerations for Combination Therapy
- Fixed-dose combinations simplify therapy and improve medication adherence compared to taking multiple separate tablets 8
- Most two-drug combinations reduce HbA1c by approximately 1 percentage point 3
- The additional glucose-lowering effect is more marked when an SGLT2 inhibitor is added to a DPP-4 inhibitor than the reverse 7, 8
- Drug-drug pharmacokinetic interaction studies show no significant changes in peak concentrations or total exposure when SGLT2 inhibitors and DPP-4 inhibitors are administered together 7
Cost Comparison
- Metformin remains the most cost-effective option at $1-3 per month for generic immediate-release formulations 1
- Sulfonylurea combinations are the most affordable add-on therapy at $2-13 per month 1
- SGLT2 inhibitor and GLP-1 receptor agonist combinations are the most expensive at $312-1,030 per month but provide cardiovascular and renal benefits 1, 6