Effect of insulin degludec versus insulin glargine U100 on time in range: SWITCH PRO, a crossover study of basal insulin-treated adults with type 2 diabetes and risk factors for hypoglycaemia

Ronald M Goldenberg, Vanita R Aroda, Liana K Billings, A Sia Louise Christiansen, Anders Meller Donatsky, Ehsan Parvaresh Rizi, Gracjan Podgorski, Katarina Raslova, David C Klonoff, Richard M Bergenstal, Ronald M Goldenberg, Vanita R Aroda, Liana K Billings, A Sia Louise Christiansen, Anders Meller Donatsky, Ehsan Parvaresh Rizi, Gracjan Podgorski, Katarina Raslova, David C Klonoff, Richard M Bergenstal

Abstract

Aims: To compare time in range (TIR) with use of insulin degludec U100 (degludec) versus insulin glargine U100 (glargine U100) in people with type 2 diabetes.

Materials and methods: We conducted a randomized, crossover, multicentre trial comparing degludec and glargine U100 in basal insulin-treated adults with type 2 diabetes and ≥1 hypoglycaemia risk factor. There were two treatment periods, each with 16-week titration and 2-week maintenance phases (with evaluation of glucose using blinded professional continuous glucose monitoring). The once-weekly titration (target: 3.9-5.0 mmol/L) was based on pre-breakfast self-measured blood glucose. The primary endpoint was percentage of TIR (3.9─10.0 mmol/L). Secondary endpoints included overall and nocturnal percentage of time in tight glycaemic range (3.9-7.8 mmol/L), and mean glycated haemoglobin (HbA1c) and glucose levels.

Results: At baseline, participants (n = 498) had a mean (SD) age of 62.8 (9.8) years, a diabetes duration of 15.1 (7.7) years and an HbA1c level of 59.6 (11.0) mmol/mol (7.6 [1.0]%). Noninferiority and superiority were confirmed for degludec versus glargine U100 for the primary endpoint, with a mean TIR of 72.1% for degludec versus 70.7% for glargine U100 (estimated treatment difference [ETD] 1.43% [95% confidence interval (CI): 0.12, 2.74; P = 0.03] or 20.6 min/d). Overall time in tight glycaemic range favoured degludec versus glargine U100 (ETD 1.5% [95% CI: 0.15, 2.89] or 21.9 min/d). Degludec also reduced nocturnal time below range (TBR; <3.9 mmol/L) compared with glargine U100 (ETD -0.88% [95% CI: -1.34, -0.42] or 12.7 min/night; post hoc) and significantly fewer nocturnal hypoglycaemic episodes of <3.0 mmol/L were observed.

Conclusions: Degludec, compared with glargine U100, provided more TIR and time in tight glycaemic range, and reduced nocturnal TBR in insulin-treated people with type 2 diabetes.

Trial registration: ClinicalTrials.gov NCT03687827.

Keywords: basal insulins; insulin analogues; insulin treatment; long-acting basal insulin; professional CGM; type 2.

Conflict of interest statement

R.G. has received research support from Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Janssen, Medtronic, Merck, Novartis, Novo Nordisk, Roche, Sanofi and Takeda, has served on advisory panels for AstraZeneca, Boehringer Ingelheim, Eli Lilly, HLS Therapeutics, Janssen, Merck, Novo Nordisk, Roche, Sanofi and Takeda, and on speaker bureaus for Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly, HLS Therapeutics, Janssen, Merck, Novo Nordisk, Sanofi and Servier, and reports consulting for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk and Takeda. V.R.A. has received research support from AstraZeneca/BMS, Boehringer Ingelheim, Calibra, Eisai, Fractyl, Janssen, Novo Nordisk, Sanofi and Theracos, and has served as a consultant for Adocia, Applied Therapeutics, AstraZeneca, Becton Dickinson, Duke, Medscape, IMNE, Liberum, Novo Nordisk, Sanofi, Tufts and Zafgen; V.R.A.'s spouse has been an employee of Merck and Janssen, receiving employee benefits. L.K.B. has received consultancy fees from Novo Nordisk, Sanofi and Eli Lilly. A.S.L.C. is an employee of Novo Nordisk and holds shares. A.MD. and E.PR. are employees of Novo Nordisk. G.P. has served on a scientific advisory board for Eli Lilly. K.R. has received financial support from Sanofi, Amgen, Novo Nordisk and Mylan for consultancy, board membership, honoraria and travel fees; and also reports grant support from Sanofi for her institution. D.C.K. is a consultant to Eoflow, Fractyl, Lifecare, Novo Nordisk, Roche Diagnostics, Samsung and Thirdwayv. R.M.B. has received research support from, consulted for or has been on a scientific advisory board for Abbott Diabetes Care, Ascensia, Dexcom, Eli Lilly, Hygieia, Johnson & Johnson, Medtronic, Novo Nordisk, Onduo, Roche, Sanofi and United Healthcare. R.M.B.'s employer, nonprofit HealthPartners Institute, contracts for his services, and no personal income goes to him.

© 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

FIGURE 1
FIGURE 1
Study design. Degludec, insulin degludec 100 U/mL; CGM, continuous glucose monitoring (Abbott FreeStyle Libre Pro); glargine U100, insulin glargine 100 U/mL; OAD, oral antidiabetic drug; OD, once daily
FIGURE 2
FIGURE 2
CONSORT flow diagram for the SWITCH PRO trial (NCT03687827). †20 participants were excluded from the final analysis set due to insufficient CGM data. Final analysis set: participants who completed the trial with full CGM assessments equaling a minimum of 10 days' CGM data per maintenance period. CGM, continuous glucose monitoring; glargine U100, insulin glargine 100 U/mL

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Source: PubMed

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