Sustained reductions in weight and HbA1c with dapagliflozin: long-term results from phase III clinical studies in type 2 diabetes

Bailey, C.J.; Wilding, J.; Nauck, M.A.; Ferranninin, E.; Ptaszynska, A.A.; Apanovitch, A.M.; Sugg, J. and Parikh, S.J. (2012). Sustained reductions in weight and HbA1c with dapagliflozin: long-term results from phase III clinical studies in type 2 diabetes. Diabetologia, 55 (Suppl.), S295.

Abstract

Background and aims: Dapagliflozin (DAPA), a selective inhibitor of sodium glucose co-transporter 2 (SGLT2), reduces plasma glucose independently of insulin secretion or action, by increasing urinary glucose excretion. In clinical trials up to 2 years, DAPA was associated with a reduction in total body weight (TBW), a key management goal in type 2 diabetes (T2D). This analysis reports TBW and HbA1cfrom four phase III clinical trials of DAPA, in predominantly overweight/obese patients with T2D, with different treatment backgrounds, and at different stages of disease.Materials and methods: The effect of DAPA (10 mg/d) on TBW and HbA1cwas assessed in four randomised, double-blind, placebo- (PBO) or comparator-controlled trials: DAPA monotherapy vs PBO (102 wks); DAPA add-on to metformin (MET) [DAPA+MET] vs PBO+MET (102 wks); DAPA+MET vs glipizide (GLIP)+MET (104 wks); DAPA+insulin (INS) [DAPA+INS] vs PBO+INS (104 wks).Results: In all DAPA groups, the significant reductions in TBW and HbA1cobserved at the end of the 24-wk short-term study were sustained for up to 2 years (Figure). At 102/104 wks, DAPA was associated with clinically meaningful reductions in TBW from baseline (BL) in each study (range: -1.74 to -4.05 kg). In contrast, over the same time period, weight gain from BL was observed in the PBO+MET (+1.36 kg), GLIP+MET (+1.36 kg) and PBO+INS (+0.91 kg) groups. PBO- or comparator-corrected adjusted mean reductions in TBW were in the range -2.41 to -5.06 kg. In addition, DAPA produced clinically meaningful reductions in HbA1c from BL (range: -0.32 to -0.78%), with PBO- or comparator-corrected adjusted mean reductions in HbA1c in the range -0.18 to -0.80%. In the DAPA groups, systolic blood pressure was either reduced or maintained in all studies (mean change from BL; range: -0.3 to -5.9 mmHg). Urinary glucose/creatinine ratio was elevated and maintained in all studies, supporting the long-term efficacy of DAPA as an SGLT2 inhibitor. Ad-verse events were generally balanced across the groups. DAPA (10 mg/d) was not associated with a higher risk of hypoglycaemia. Events suggestive of genital and urinary tract infection were greater with DAPA. Infections occurred more often in the first 24 wks, were mostly mild to moderate in severity, man-aged by standard interventions, and without serious clinical consequences. Conclusion: In populations of overweight/obese patients with T2D, treated across the typical course of the disease, DAPA administered as monotherapy or in combination with MET or INS was associated with sustained decreases in both TBW and HbA1c, over 2 years.

Publication DOI: https://doi.org/10.1007/s00125-012-2688-9
Divisions: Life & Health Sciences > Biosciences
Additional Information: Abstracts of the 48th EASD (European Association for the Study of Diabetes) Annual Meeting of the European Association for the Study of Diabetes. October 1-5, 2012. Berlin, Germany
Uncontrolled Keywords: diabetes mellitus
Published Date: 2012-10

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