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Initial empagliflozin, metformin combination reduces HbA1c in type 2 diabetes
Patients with poorly controlled type 2 diabetes assigned a combination of empagliflozin and metformin as first-line therapy saw greater decreases in HbA1c vs. patients assigned either empagliflozin or metformin monotherapy, recent findings suggest.
“Empagliflozin + metformin combinations could be a useful treatment regimen to provide rapid, clinically relevant improvements in glycemic control in newly diagnosed patients with type 2 diabetes,” Samy Hadjadj, MD, PhD, professor of endocrinology and diabetes at the University of Poitiers and a consultant endocrinologist at Poitiers University Hospital in France, and colleagues wrote. “Importantly, 57% to 70% of patients with an HbA1c 7% at baseline who received combination therapy reached [an] HbA1c < 7% at week 24, and 37% to 52% reached [an] HbA1c < 6.5%.”
Hadjadj and colleagues analyzed data from 1,364 drug-naive patients with an HbA1c greater than 7.5% randomly assigned for 24 weeks to empagliflozin (Jardiance, Boehringer Ingelheim) 12.5 mg twice daily plus metformin 1,000 mg twice daily; empagliflozin 12.5 mg twice daily plus metformin 500 mg twice daily; empagliflozin 5 mg twice daily plus metformin 1,000 mg twice daily; empagliflozin 5 mg twice daily plus metformin 500 mg twice daily; empagliflozin 25 mg once daily; empagliflozin 10 mg once daily; metformin 1,000 mg twice daily; or metformin 500 mg twice daily. Study visits were scheduled for baseline and weeks 6, 12, 18 and 24, plus a follow-up visits 7 days after last intake of study drug. Primary endpoint was change from baseline in HbA1c at week 24.
At week 24, participants across treatment groups all experienced reductions in HbA1c. Compared with empagliflozin once-daily regimens, researchers found that adjusted mean differences in changes from baseline with combination empagliflozin plus metformin twice daily ranged from a reduction of 0.57% to 0.72% (P < .001); the reduction ranged from a mean of 0.33% to 0.79% when compared with metformin twice-daily regimens (P < .001).
Adjusted mean HbA1c values for combination therapy ranged from 6.6% (empagliflozin 5 mg or 12.5 mg plus metformin 1,000 mg twice daily) to 6.7% (empagliflozin 12.5 mg plus metformin 500 mg twice daily) vs. 7.3% for both empagliflozin 10 mg and 25 mg once daily and 7.5% and 6.9% for metformin 500 mg and 1,000 mg once daily, respectively. Participants assigned combination therapy also saw greater reductions in weight and fasting plasma glucose. Adverse events were rare, including confirmed hypoglycemia-related adverse events across groups (0%-1.8%).
Patients assigned combination therapy also saw greater reductions in blood pressure vs. metformin monotherapy groups, but not compared with empagliflozin monotherapy groups.
“This was as expected given that empagliflozin has consistently been shown to reduce BP in patients with type 2 diabetes,” the researchers wrote. “The mechanisms behind reductions in BP with empagliflozin have not been fully clarified but may reflect weight loss, volume contraction secondary to osmotic diuresis or arterial stiffness.”
The researchers noted that recent findings from the landmark EMPA-REG trial may encourage earlier use of combinations including empagliflozin in patients with type 2 diabetes and high cardiovascular risk. – by Regina Schaffer
Disclosure: Hadjadj reports serving as a consultant or on advisory panels for AstraZeneca and Bristol-Myers Squibb; receiving honoraria or speaking fees from Abbott, AstraZeneca/Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novo Nordisk, Sanofi, Servier and Takeda; research grants from Abbott and Takeda; and travel grants from AstraZeneca/Bristol-Myers Squibb, Janssen, Merck Sharp & Dohme and Sanofi. Please see the full study for the other authors’ relevant financial disclosures.