Incidence of genital tract infections (GTIs), a common adverse event during SGLT2 inhibitor therapy, may be modified by concomitant DPP-4 inhibitor treatment. We evaluated GTI incidence across randomized trials of dapagliflozin (DAPA) ± saxagliptin (SAXA) as add-on to metformin (MET). Safety data were pooled from seven randomized phase 3 trials; patients with type 2 diabetes (N=3134) receiving DAPA 5/10 mg, SAXA 5 mg or DAPA 5/10 mg + SAXA 5 mg as add-on to MET for 24-52 weeks were included. Data from patients with 52 weeks of follow-up across five of the studies were pooled separately (long-term [LT]-study pool; N=1719). In the 7-study pool, GTI incidence was lower with add-on DAPA 10 mg + SAXA 5 mg to MET vs. add-on of DAPA 10 mg alone (3.6% vs. 6.6%); the most common events in both groups were vulvovaginal mycotic infections (DAPA + SAXA, 1.5%; DAPA, 2.0%) and balanoposthitis (DAPA + SAXA, 0.9%; DAPA, 1.8%) (Table). This finding was confirmed in the individual studies with the exception of one study comparing GTI incidence with low-dose DAPA 5 mg + SAXA 5 mg (3.1%) vs. DAPA 5 mg (1.4%). With LT treatment, GTI incidence decreased over time with DAPA 10 mg + SAXA 5 mg and DAPA 10 mg (month 6, 3.1% and 5.3%; month 12, 0.9% and 2.1%).

In conclusion, add-on of DAPA 10 mg + SAXA 5 mg to MET led to lower GTI incidence than with DAPA 10 mg alone; this effect was maintained after 12 months of treatment.

graphic
View largeDownload slide
Disclosure

S. Del Prato: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, GlaxoSmithKline plc., Intarcia Therapeutics, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Servier, Sanofi, Takeda Pharmaceuticals U.S.A., Inc.. Research Support; Self; Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Takeda Pharmaceuticals U.S.A., Inc.. Advisory Panel; Self; Janssen Biotech, Inc., Abbott. E.K. Johnsson: Employee; Self; AstraZeneca. R. Garcia-Sanchez: Employee; Self; AstraZeneca. C. Morgan: Employee; Self; AstraZeneca. P. Sartipy: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca, Novo Nordisk A/S. R. Kurlyandskaya: Employee; Self; AstraZeneca. N. Iqbal: Employee; Self; AstraZeneca. C. Mathieu: Research Support; Self; Novo Nordisk A/S. Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S. Research Support; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Advisory Panel; Self; Sanofi. Research Support; Self; Merck Sharp & Dohme Corp.. Speaker's Bureau; Self; Merck Sharp & Dohme Corp.. Advisory Panel; Self; Merck Sharp & Dohme Corp.. Research Support; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Advisory Panel; Self; Eli Lilly and Company. Research Support; Self; Novartis AG. Speaker's Bureau; Self; Novartis AG. Advisory Panel; Self; Novartis AG, Bristol-Myers Squibb Company. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; AstraZeneca, Pfizer Inc., Janssen Pharmaceuticals, Inc., Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Boehringer Ingelheim GmbH. Advisory Panel; Self; Hanmi Pharmaceutical. Research Support; Self; Roche Diagnostics Corporation. Advisory Panel; Self; Roche Diagnostics Corporation. Research Support; Self; Medtronic. Advisory Panel; Self; Medtronic, MannKind Corporation. Research Support; Self; Intrexon. Advisory Panel; Self; Intrexon, Dianax, UCB, Inc.. Research Support; Self; Abbott.

© 2018 by the American Diabetes Association.
2018
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.