Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2020 Jul;22(7):1083-1093.
doi: 10.1111/dom.13997. Epub 2020 Mar 9.

Efficacy and safety of dual add-on therapy with dapagliflozin plus saxagliptin versus glimepiride in patients with poorly controlled type 2 diabetes on a stable dose of metformin: Results from a 52-week, randomized, active-controlled trial

Juan P Frias  1 , Guillermo Gonzalez-Galvez  2 , Eva Johnsson  3 , Jill Maaske  4 , Marcia A Testa  5 , Donald C Simonson  6   7 , Nalina Dronamraju  3 , Ricardo Garcia-Sanchez  4 , Anne L Peters  8
Affiliations
Randomized Controlled Trial

Efficacy and safety of dual add-on therapy with dapagliflozin plus saxagliptin versus glimepiride in patients with poorly controlled type 2 diabetes on a stable dose of metformin: Results from a 52-week, randomized, active-controlled trial

Juan P Frias et al. Diabetes Obes Metab. 2020 Jul.

Abstract

Aims: To evaluate the efficacy and safety of dapagliflozin (DAPA) + saxagliptin (SAXA) compared with glimepiride (GLIM) in patients with type 2 diabetes who were inadequately controlled [glycated haemoglobin (HbA1c) 7.5-10.5% (58-91 mmol/mol)] on metformin monotherapy.

Materials and methods: This 52-week, multicentre, double-blind, active-controlled study (NCT02419612) randomized (1:1) patients on metformin to add-on DAPA 10 mg + SAXA 5 mg (n = 227) or GLIM 1-6 mg (titrated; n = 217). The primary efficacy endpoint was change in HbA1c from baseline to week 52.

Results: Baseline mean ± standard deviation of age, duration of diabetes and HbA1c were 56.1 ± 9.7 years, 7.8 ± 6.4 years and 8.5% ± 0.8% (69 ± 9.0 mmol/mol), respectively. Adjusted mean change from baseline in HbA1c was -1.35% (-14.8 mmol/mol) with DAPA + SAXA versus -0.98% (-10.7 mmol/mol) with GLIM (P <0.001). Changes from baseline in body weight and systolic blood pressure were -3.1 kg and -2.6 mmHg with DAPA + SAXA versus +1.0 kg (P <0.001) and +1.0 mmHg (P = 0.007) with GLIM. More patients achieved HbA1c <7.0% (53 mmol/mol) (44.3% vs. 34.3%; P = 0.044), and fewer patients required treatment intensification (1.3% vs. 8.8%; P = 0.002) with DAPA + SAXA than with GLIM.

Conclusions: Compared with GLIM, concurrent addition of DAPA + SAXA significantly improved glycaemic control, body weight and other metabolic parameters in patients inadequately controlled on metformin. Trial: NCT02419612, ClinicalTrials.gov.

Keywords: dapagliflozin; glimepiride; glycaemic control; intensification; metformin; saxagliptin.

PubMed Disclaimer

Conflict of interest statement

J.F. has received research support from Allergan, AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, Genentech, IONIS, Janssen, Lexicon, Ligand, Merck, Novartis, Novo Nordisk, Pfizer, Sanofi and Theracos. He has participated in advisory boards and received consulting fees from Eli Lilly, Johnson & Johnson, Merck, Novo Nordisk and Sanofi. G.G. is an advisory board member and speaker for Amgen, AstraZeneca, Janssen, MSD, Novo Nordisk, Sanofi, Stendhal and Takeda. A.P. has participated as an advisor for Abbott Diabetes Care, Boehringer Ingelheim, Eli Lilly and Company, Medscape, Mannkind, Novo Nordisk, and Sanofi. She has also received research support from Dexcom and vTv. She has stock options from Mellitus Health, Omada Health, Stability Health, Pendulum Therapeutics, and Livongo. M.T. is a board member of, and a stockholder in, Phase V Technologies, Inc. D.S. is a board member of Phase V Technologies, Inc. and a stockholder in GI Windows. J.M. and E.J. are employees of and stockholders in AstraZeneca. R.G. was an employee of AstraZeneca at the time of the study but as of publication is an employee of Bristol‐Myers Squibb; R.G. is a stockholder in AstraZeneca. N.D. is an employee of AstraZeneca.

Figures

Figure 1
Figure 1
A, Adjusted mean change from baseline to week 52 in HbA1c. B, Adjusted mean change from baseline in HbA1c during the 52‐week, double‐blind treatment period (randomized analysis set). N refers to the number of patients in each group who were randomized and received at least one dose of treatment with the study drug; n denotes the number of patients with available measurements at baseline and week 52. †All values are least‐squares mean ± standard error. ‡ P‐value obtained using a mixed model of repeated measures with terms for treatment, baseline HbA1c, week, treatment‐by‐week interaction and baseline HbA1c‐by‐week interaction. Abbreviations: CI, confidence interval; DAPA, dapagliflozin; GLIM, glimepiride; HbA1c, glycated haemoglobin; MET, metformin; SAXA, saxagliptin
Figure 2
Figure 2
A, Proportion of patients with HbA1c <7.0% (53 mmol/mol) at week 52. B, Adjusted mean change from baseline in total body weight during the 52‐week, double‐blind treatment period. C, Adjusted mean change from baseline in SBP at week 52. N refers to the number of patients in each group who were randomized and received at least one dose of treatment with the study drug; n denotes the number of patients with available measurements at baseline and week 52. In the analysis of patients with HbA1c <7.0% (53 mmol/mol) at week 52, patients with an unknown status at week 52 and patients rescued before week 52 were treated as non‐responders. †MMRM model with terms for treatment, baseline body weight/SBP, week, treatment‐by‐week interaction and baseline body weight/SBP‐by‐week interaction. ‡Logistic regression method with adjustment for baseline HbA1c. Abbreviations: CI, confidence interval; DAPA, dapagliflozin; GLIM, glimepiride; HbA1c, glycated haemoglobin; MET, metformin; MMRM, mixed model of repeated measures; SAXA, saxagliptin; SBP, systolic blood pressure; SE, standard error
See this image and copyright information in PMC

References

    1. Fonseca VA. Defining and characterizing the progression of type 2 diabetes. Diabetes Care. 2009;32(Suppl 2):S151‐S156. - PMC - PubMed
    1. American Diabetes Association. Standards of medical care in diabetes – 2017. Diabetes Care. 2017;40(Suppl 1):S1‐S132. - PubMed
    1. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycaemia in type 2 diabetes, 2015: A patient‐centred approach. Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia. 2015;58:429‐442. - PubMed
    1. Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the american association of clinical endocrinologists and american college of endocrinology on the comprehensive type 2 diabetes management algorithm ‐ 2017 executive summary. Endocr Pract. 2017;23:207‐238. - PubMed
    1. Sola D, Rossi L, Schianca GP, et al. Sulfonylureas and their use in clinical practice. Arch Med Sci. 2015;11:840‐848. - PMC - PubMed

Publication types

Associated data