Sotagliflozin in Combination With Optimized Insulin Therapy in Adults With Type 1 Diabetes: The North American inTandem1 Study

Buse, John B.; Garg, Satish K.; Rosenstock, Julio; Bailey, Timothy S.; Banks, Phillip; Bode, Bruce W.; Danne, Thomas; Kushner, Jake A.; Lane, Wendy; Lapuerta, Pablo; McGuire, Darren K.; Peters, Anne L.; Reed, John H.; Sawhney, Sangeeta; Strumph, Paul

doi:10.2337/dc18-0343

Cited by 172 publications

(303 citation statements)

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“…ClinicalTrials was also searched and no additional clinical trials with reported results could be found. Finally, in total, 13 eligible studies with 5397 participants (3364 participants in intervention groups vs 2033 participants in control groups) were enrolled, including two articles in one RCT for canagliflozin, four articles for dapagliflozin, four articles for empagliflozin (three articles in one RCT) and six articles for sotagliflozin . Most of the articles showed a relative low risk bias, but other bias with a higher risk was because nine studies were funded …”

Section: Resultsmentioning

confidence: 99%

Safety and efficacy of sodium glucose co‐transporter 2 inhibitors combined with insulin in adults with type 1 diabetes: A meta‐analysis of randomized controlled trials

2019

Journal of Diabetes

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Background The safety and efficacy of sodium glucose co‐transporter 2 (SGLT2) inhibitors in a dose‐dependent manner for type 1 diabetes mellitus (T1DM) are unclear. Methods Randomized clinical trials (RCT) were searched from PubMed, EMBASE, the Cochrane Library, Web of Science and ClinicalTrials until August 2018. Results Thirteen RCT with 5397 participants were included. SGLT2 inhibitors were proved to be effective in glycemic control and weight loss in T1DM. In the subgroups of different doses, SGLT2 inhibitors exhibited reductions in glycated haemoglobin, bodyweight, fasting plasma glucose, mean daily glucose, basal insulin dose, bolus insulin dose, estimated glomerular filtration rate and systolic blood pressure, and elevations in the mean amplitude of glucose excursions, and percentage of time in target glucose range in a dose‐dependent manner. Reductions in total insulin dose and urinary glucose excretion were dose‐independent. SGLT2 inhibitors did not induce hypoglycemia, severe hypoglycemia, cardiovascular events, bone fracture and all‐cause mortality, but increased the risk of adverse events (AE), adverse events related to the drug treatment, infections, diabetic ketoacidosis (DKA) and renal disease correlated with dosage. Conclusions SGLT2 inhibitors in high and moderate doses can achieve a better outcome on efficacy, but may induce a higher risk of adverse events, especially DKA.

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Section: Resultsmentioning

confidence: 99%

Safety and efficacy of sodium glucose co‐transporter 2 inhibitors combined with insulin in adults with type 1 diabetes: A meta‐analysis of randomized controlled trials

2019

Journal of Diabetes

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“…This is in line with recent studies showing an association between patients' glycaemic status and weight loss, 39 and may result from higher levels of Total GTL P-Levels of incretin hormones, GLP-1, PYY 3-36 and GIP following treatment with licogliflozin in patients with T2DM. Multiple clinical studies have been conducted to assess the efficacy and safety of sotagliflozin in patients with diabetes 26,[43][44][45]. (n = 15/cohort).…”

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confidence: 99%

The effects of licogliflozin, a dual SGLT1/2 inhibitor, on body weight in obese patients with or without diabetes

He¹,

Haynes

Meyers³

et al. 2019

Diabetes Obesity Metabolism

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BACKGROUND: There is an unmet need for a safer and more effective treatment for obesity.This study assessed the effects of licogliflozin, a dual inhibitor of sodium-glucose co-transporter (SGLT) 1/2, on body weight, metabolic parameters and incretin hormones in patients with type 2 diabetes mellitus (T2DM) and/or obesity. METHODS:Patients with obesity (BMI, 35-50 kg/m 2 ) were enrolled into a 12-week study (N = 88; licogliflozin 150 mg q.d.). Patients with T2DM were enrolled into a second, two-part study, comprising a single-dose cross-over study (N = 12; 2.5 − 300 mg) and a 14-day dosing study (N = 30; 15 mg q.d). Primary endpoints included effects on body weight, effects on glucose, safety and tolerability. Secondary endpoints included urinary glucose excretion (UGE 24 ) and pharmacokinetics, while exploratory endpoints assessed the effects on incretin hormones (total GLP-1, PYY 3-36 , and GIP), insulin and glucagon.RESULTS: Treatment with licogliflozin 150 mg q.d. for 12 weeks in patients with obesity significantly reduced body weight by 5.7% vs placebo (P < 0.001) and improved metabolic parameters such as significantly reduced postprandial glucose excursion (21%; P < 0.001), reduced insulin levels (80%; P < 0.001) and increased glucagon (59%; P < 0.001). In patients with T2DM, a single dose of licogliflozin 300 mg in the morning prior to an oral glucose tolerance test (OGTT) remarkably reduced glucose excursion by 93% (P < 0.001; incremental AUC 0-4h ) and suppressed insulin by 90% (P < 0.01; incremental AUC 0-4h ). Treatment with licogliflozin 15 mg q.d. for 14 days reduced 24-hour average glucose levels by 26% (41 mg/dL; P < 0.001) and increased UGE 24 to 100 g (P < 0.001) in patients with T2DM. In addition, this treatment regimen significantly increased total GLP-1 by 54% (P < 0.001) and PYY 3-36 by 67% (P < 0.05) post OGTT vs placebo, while significantly reducing GIP levels by 53% (P < 0.001). Treatment with licogliflozin was generally safe and well tolerated. Diarrhea (increased numbers of loose stool) was the most common adverse event in all studies (90% with licogliflozin vs 25% with placebo in the 12-week study), while a lower incidence of flatulence, abdominal pain and abdominal distension (25%-43% with licogliflozin vs 9%-11% with placebo in the 12-week study) were among the other gastrointestinal events reported. CONCLUSION: Licogliflozin treatment (1-84 days) leads to significant weight loss and favourable changes in a variety of metabolic parameters and incretin hormones. Dual inhibition of SGLT1/2 with licogliflozin in the gut and kidneys is an attractive strategy for treating obesity and diabetes. K E Y W O R D S clinical trial, continuous glucose monitoring (CGM), incretins, obesity therapy, phase I-II study, weight control

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“…She challenged the DKA protocols used in SGLT‐2 inhibitor clinical trials: (a) inTandem for sotagliflozin, (b) Dapagliflozin Evaluation in Patients with Inadequately Controlled Type 1 Diabetes (DEPICT) for dapagliflozin, and (c) Empagliflozin as Adjunctive to Insulin Therapy (EASE) for empagliflozin, stating that they did not adequately emphasize DKA prevention. This opinion was based on these trial protocols' high baseline HbA1c ranges and lack of exclusion criteria based on baseline beta‐hydroxybutyrate levels . Dr Peters' personal approach for off‐label use of SGLT‐2 inhibitors involves only including patients with a baseline HbA1c less than 9%, baseline ketone levels below 0.6 mmol/L, starting SGLT‐2 inhibitor treatment at the lowest dose, not changing insulin dosage, and continuing with morning ketone testing until the maximum, stable dose is reached.…”

Section: Practical Ways To Achieve Targets In Diabetes Care Conferencementioning

confidence: 99%

Practical ways to achieve targets in diabetes care conference

Biba

Teng

Kurian

et al. 2019

Journal of Diabetes

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Ursula Biba, Rhea W. Teng, Martin J. Kurian, and Kelly L. Close are of Close Concerns (http://www.closeconcerns.com), a healthcare information company focused exclusively on diabetes and obesity care. Close Concerns publishes Closer Look, a periodical that brings together news and insights in these areas. Each month, the Journal of Diabetes includes this News feature, in which Biba, Teng, Kurian, and Close review the latest developments relevant to researchers and clinicians.

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Sotagliflozin in Combination With Optimized Insulin Therapy in Adults With Type 1 Diabetes: The North American inTandem1 Study

Cited by 172 publications

References 41 publications

Safety and efficacy of sodium glucose co‐transporter 2 inhibitors combined with insulin in adults with type 1 diabetes: A meta‐analysis of randomized controlled trials

Safety and efficacy of sodium glucose co‐transporter 2 inhibitors combined with insulin in adults with type 1 diabetes: A meta‐analysis of randomized controlled trials

The effects of licogliflozin, a dual SGLT1/2 inhibitor, on body weight in obese patients with or without diabetes

Practical ways to achieve targets in diabetes care conference

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