Sotagliflozin (SOTA) is a dual SGLT1 and SGLT2 inhibitor in development as an adjunct to insulin in T1D.

This was a pooled analysis of the inTandem1 and inTandem2 trials in adults with T1D treated with multiple daily insulin injections or pump therapy who were randomized 1:1:1 to placebo, SOTA 200 mg or SOTA 400 mg once daily after 6 weeks of insulin optimization. Of these, 278 patients participated in a blinded continuous glucose monitoring (CGM) sub-study. The primary endpoint of this sub-study was the percentage of time in the target glucose range (70 mg/dL-180 mg/dL). Mean daily glucose and amplitude of all glycemic excursions (MAGE) of <70 and >180 mg/dL were also assessed.

Baseline characteristics were similar among groups. Compared with placebo, treatment with SOTA 200 and 400 mg significantly increased the time in range (+1.3 and +2.8 hours/day, respectively) and reduced MAGE at Week 24, while SOTA 400 mg also significantly reduced mean daily glucose (Table).

In conclusion, when used adjunctively in T1D, SOTA improved the time in target glucose range compared with placebo, demonstrating efficacy in glycemic control beyond a reduction in A1C.

    
CGM Data at Baseline and Week 24 
 Optimized insulin + placebo n=93 Optimized insulin + SOTA 200 mg n=89 Optimized insulin + SOTA 400 mg n=96 
Percentage of readings in the range of 70-180 mg/dL (3.9-10.0 mmol/L) 
Baseline mean ± SD 52 ± 14 52 ± 15 51 ± 15 
Week 24 mean ± SD 52 ± 15 58 ± 16 64 ± 14 
LS mean change from baseline ± SE -1.3 ± 1.8 +4.1 ± 1.8 +10.5 ± 1.7 
Mean change from baseline hr/day* -0.3 hr/day +1.0 hr/day +2.5 hr/day 
LS mean difference from placebo (95% CI) NA +5.4 (+0.6, +10.1) +11.7 (+7.1, +16.3) 
P-value NA 0.026 <0.001 
Mean difference from placebo hr/day* NA +1.3 hr/day +2.8 hr/day 
Mean daily glucose (mg/dL) 
Baseline mean ± SD 175 ± 31 176 ± 33 178 ± 32 
Week 24 mean ± SD 176 ± 32 167 ± 32 156 ± 23 
LS mean change from baseline ± SE +2.0 ± 3.6 -5.9 ± 3.6 -16.9 ± 3.4 
LS mean difference from placebo (95% CI) NA -7.9 (-17.2, +1.3) -18.9 (-27.9, -9.9) 
P-value NA 0.09 <0.001 
MAGE mg/dL 
Baseline mean ± SD 166 ± 35 163 ± 34 158 ± 36 
Week 24 mean ± SD 159 ± 32 146 ± 38 131 ± 33 
LS mean change from baseline ± SE -3.0 ± 4.2 -15.7 ± 4.2 -25.1 ± 3.9 
LS mean difference from placebo (95% CI) NA -12.7 (-23.6, -1.8) -22.1 (-32.7, -11.5) 
P-value NA 0.022 <0.001 
CGM, continuous glucose monitoring; CI, confidence interval; LS, least squares, MAGE; mean amplitude of glucose excursion, NA; not applicable; SD, standard deviation; SE, standard error. Statistical comparisons of each SOTA arm with placebo were pre-planned and performed using a generalized linear model with repeated measures statistics; *Assuming 100% daily CGM data available for analysis, 1.0% of daily CGM time = 0.24 hours. 
    
CGM Data at Baseline and Week 24 
 Optimized insulin + placebo n=93 Optimized insulin + SOTA 200 mg n=89 Optimized insulin + SOTA 400 mg n=96 
Percentage of readings in the range of 70-180 mg/dL (3.9-10.0 mmol/L) 
Baseline mean ± SD 52 ± 14 52 ± 15 51 ± 15 
Week 24 mean ± SD 52 ± 15 58 ± 16 64 ± 14 
LS mean change from baseline ± SE -1.3 ± 1.8 +4.1 ± 1.8 +10.5 ± 1.7 
Mean change from baseline hr/day* -0.3 hr/day +1.0 hr/day +2.5 hr/day 
LS mean difference from placebo (95% CI) NA +5.4 (+0.6, +10.1) +11.7 (+7.1, +16.3) 
P-value NA 0.026 <0.001 
Mean difference from placebo hr/day* NA +1.3 hr/day +2.8 hr/day 
Mean daily glucose (mg/dL) 
Baseline mean ± SD 175 ± 31 176 ± 33 178 ± 32 
Week 24 mean ± SD 176 ± 32 167 ± 32 156 ± 23 
LS mean change from baseline ± SE +2.0 ± 3.6 -5.9 ± 3.6 -16.9 ± 3.4 
LS mean difference from placebo (95% CI) NA -7.9 (-17.2, +1.3) -18.9 (-27.9, -9.9) 
P-value NA 0.09 <0.001 
MAGE mg/dL 
Baseline mean ± SD 166 ± 35 163 ± 34 158 ± 36 
Week 24 mean ± SD 159 ± 32 146 ± 38 131 ± 33 
LS mean change from baseline ± SE -3.0 ± 4.2 -15.7 ± 4.2 -25.1 ± 3.9 
LS mean difference from placebo (95% CI) NA -12.7 (-23.6, -1.8) -22.1 (-32.7, -11.5) 
P-value NA 0.022 <0.001 
CGM, continuous glucose monitoring; CI, confidence interval; LS, least squares, MAGE; mean amplitude of glucose excursion, NA; not applicable; SD, standard deviation; SE, standard error. Statistical comparisons of each SOTA arm with placebo were pre-planned and performed using a generalized linear model with repeated measures statistics; *Assuming 100% daily CGM data available for analysis, 1.0% of daily CGM time = 0.24 hours. 

Disclosure

T. Danne: Speaker's Bureau; Self; A. Menarini Diagnostics. Advisory Panel; Self; Abbott, AstraZeneca, Bayer AG, Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Dexcom, Inc.. Research Support; Self; Eli Lilly and Company. Stock/Shareholder; Self; DreaMed Diabetes, Ltd.. Research Support; Self; Insulet Corporation. Speaker's Bureau; Self; Menarini Group. B. Cariou: Board Member; Self; Amgen Inc.. Consultant; Self; Genfit. Board Member; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Merck Sharp & Dohme Corp.. Board Member; Self; Sanofi-Aventis, Regeneron Pharmaceuticals, Inc. J.B. Buse: Other Relationship; Self; ADOCIA, AstraZeneca, Dexcom, Inc., Elcelyx Therapeutics, Inc., Eli Lilly and Company, Fractyl Laboratories, Inc., Intarcia Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Metavention, NovaTarg, Novo Nordisk A/S, Sanofi, VTV Therapeutics. Research Support; Self; Boehringer Ingelheim GmbH, Johnson & Johnson Services, Inc., Theracos, Inc.. Other Relationship; Self; Shenzhen Hightide Biopharmaceutical, Ltd.. Research Support; Self; National Heart, Lung, and Blood Institute, National Center for Advancing Translational Sciences. Other Relationship; Self; National Institute of Diabetes and Digestive and Kidney Diseases, American Diabetes Association. Research Support; Self; Patient-Centered Outcomes Research Institute. Other Relationship; Self; National Institute of Environmental Health Sciences. S.K. Garg: Research Support; Self; Dexcom, Inc., Eli Lilly and Company, Sanofi US. Advisory Panel; Self; Sanofi US. Research Support; Self; MannKind Corporation, Diasome Pharmaceuticals, Inc., Labstyle Innovations, Lexicon Pharmaceuticals, Inc., Medtronic. Advisory Panel; Self; Novo Nordisk A/S. J. Rosenstock: Advisory Panel; Self; Eli Lilly and Company. Consultant; Self; Eli Lilly and Company. Research Support; Self; Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. Advisory Panel; Self; Sanofi. Consultant; Self; Sanofi. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Consultant; Self; Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; Intarcia Therapeutics, Inc.. Consultant; Self; Intarcia Therapeutics, Inc.. Research Support; Self; Merck & Co., Inc., Pfizer Inc., Sanofi, Novo Nordisk Inc., Bristol-Myers Squibb Company, Eli Lilly and Company, Intarcia Therapeutics, Inc., Genentech, Inc. P.L. Banks: Employee; Self; Lexicon Pharmaceuticals, Inc. J.A. Kushner: Advisory Panel; Self; Lexicon Pharmaceuticals, Inc.. Consultant; Self; KNOW Foods, Inc. D.K. McGuire: Consultant; Self; AstraZeneca, Sanofi-Aventis, Eli Lilly and Company, Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Pfizer Inc., Novo Nordisk A/S. Research Support; Self; AstraZeneca, Sanofi-Aventis, Janssen Pharmaceuticals, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S, Lexicon Pharmaceuticals, Inc., Eisai Inc., GlaxoSmithKline plc., Esperion Therapeutics. A.L. Peters: Advisory Panel; Self; Abbott, Bigfoot Biomedical. Research Support; Self; Dexcom, Inc.. Advisory Panel; Self; Eli Lilly and Company, Insulin Algorithms, JDRF, Lexicon Pharmaceuticals, Inc., Livongo Health. Research Support; Self; MannKind Corporation. Other Relationship; Self; Medscape. Advisory Panel; Self; Merck & Co., Inc.. Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases. Speaker's Bureau; Self; Novo Nordisk Inc.. Advisory Panel; Self; Novo Nordisk Inc., Omada Health, Inc., Optum Rx, Inc., Sanofi. Research Support; Self; T1D Exchange. Advisory Panel; Self; The Endocrine Society. Research Support; Self; The Leona M. and Harry B. Helmsley Charitable Trust. Advisory Panel; Spouse/Partner; Johnson & Johnson Diabetes Institute, LLC. S. Sawhney: Employee; Self; Lexicon Pharmaceuticals, Inc.. Stock/Shareholder; Spouse/Partner; GlaxoSmithKline plc., AstraZeneca, Pfizer Inc., Eli Lilly and Company, Novartis Pharmaceuticals Corporation. P. Strumph: Employee; Self; Lexicon Pharmaceuticals, Inc.. Stock/Shareholder; Self; Lexicon Pharmaceuticals, Inc.. Board Member; Self; College Diabetes Network.

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