Can sitagliptin be used with dapagliflozin (Dapagliflozin) in patients with type 2 diabetes?

Sitagliptin and Dapagliflozin Combination Therapy in Type 2 Diabetes

Yes, sitagliptin can be used with dapagliflozin in patients with type 2 diabetes, and this combination is supported by clinical evidence showing improved glycemic control without significant safety concerns. 1, 2

Efficacy of Combination Therapy

• Dapagliflozin (an SGLT2 inhibitor) has been specifically studied in combination with sitagliptin (a DPP-4 inhibitor) and has demonstrated significant efficacy in improving glycemic control 1, 3
• The FDA label for dapagliflozin explicitly states that it "has been studied in adult patients in combination with sitagliptin (with or without metformin)" 1
• A real-world retrospective study showed that the fixed-dose combination of dapagliflozin and sitagliptin significantly reduced HbA1c from 8.9% to 7.2% after 12 weeks of treatment 2
• When dapagliflozin was added to sitagliptin therapy (with or without metformin), it reduced mean HbA1c levels by 0.5% compared to placebo at 24 weeks, with benefits maintained through 48 weeks 3

Cardiovascular and Renal Benefits

• According to the 2019 ESC guidelines, both medication classes have specific benefits:
  • SGLT2 inhibitors like dapagliflozin are recommended in patients with T2DM and cardiovascular disease or high CV risk to reduce cardiovascular events 4
  • DPP4 inhibitors sitagliptin and linagliptin have a neutral effect on risk of heart failure and may be considered in patients with diabetes 4
• SGLT2 inhibitors are also recommended to reduce progression of diabetic kidney disease 4
• Unlike saxagliptin (another DPP-4 inhibitor), sitagliptin is not contraindicated in patients with heart failure 4

Complementary Mechanisms of Action

• The combination provides complementary mechanisms of action:
  • Dapagliflozin works by inhibiting SGLT2 in the kidneys, increasing urinary glucose excretion and reducing hyperglycemia 4
  • Sitagliptin increases circulating incretins, which stimulate insulin secretion and inhibit glucose production 5
• This dual mechanism approach can provide better glycemic control than either agent alone 2, 3

Safety Considerations

• The combination of dapagliflozin and sitagliptin is generally well-tolerated 2, 3
• Key safety considerations include:
  • Genital infections are more common with dapagliflozin (9.8% vs 0.4% with placebo over 48 weeks) 3
  • Urinary tract infections are generally balanced between dapagliflozin and placebo 3
  • Risk of hypoglycemia is low with this combination, particularly when not used with sulfonylureas 5, 3

Special Populations

• In patients with mild renal insufficiency (eGFR 60-90 mL/min/1.73m²), a head-to-head comparison showed sitagliptin provided greater HbA1c reduction than dapagliflozin 6
• Dapagliflozin should be used with caution in patients with renal insufficiency (GFR < 45 mL/min/1.73 m²) 4
• Sitagliptin requires dose adjustment in moderate-to-severe renal impairment 5

Practical Recommendations

• When considering adding sitagliptin to dapagliflozin (or vice versa):
  • Assess renal function, as both medications have different considerations in renal impairment 4, 5
  • Monitor for genital infections, particularly in patients receiving dapagliflozin 3
  • Consider the complementary effects on insulin resistance and body fat distribution 7
• The combination may be particularly beneficial for patients not achieving glycemic targets on monotherapy 4, 2, 3

In conclusion, sitagliptin can be effectively and safely used with dapagliflozin in patients with type 2 diabetes, providing complementary mechanisms of action that improve glycemic control while maintaining favorable cardiovascular and renal profiles.