HbA1c and Hypoglycemia Reductions at 24 and 52 Weeks With Sotagliflozin in Combination With Insulin in Adults With Type 1 Diabetes: The European inTandem2 Study

Danne, Thomas; Cariou, Bertrand; Banks, Phillip; Brändle, Michael; Brath, Helmut; Franek, Edward; Kushner, Jake A.; Lapuerta, Pablo; McGuire, Darren K.; Peters, Anne L.; Sawhney, Sangeeta; Strumph, Paul

doi:10.2337/dc18-0342

Cited by 137 publications

(266 citation statements)

References 33 publications

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“…The results of this dose‐ranging study were confirmed in three larger, previously published, phase 3 trials, in which sotagliflozin significantly reduced HbA1c, weight and SBP with lower bolus and total insulin doses . A pooled analysis of data from the inTandem1 and inTandem2 studies confirmed the PPG reductions seen in the present study .…”

Section: Discussionsupporting

confidence: 87%

“…All patients received urine ketone strips and blood BHB meters and strips, as well as instructions on detecting and treating ketosis, urogenital hygiene, and proper hydration. Study centres received recommendations for ketosis and DKA diagnosis and management, as detailed in the phase 3 sotagliflozin trial reports (inTandem1, 2 and 3) …”

Section: Methodsmentioning

confidence: 99%

“…Although pramlintide is approved as an insulin adjunct and may reduce weight as well as glycated haemoglobin (HbA1c), it requires multiple daily injections (MDI) and may increase the risk of severe hypoglycaemia . Oral sodium‐glucose co‐transporter (SGLT) inhibitors, when combined with insulin for the treatment of T1D, represent a possible approach to improving glycaemic control without increasing weight or hypoglycaemic events …”

Section: Introductionmentioning

confidence: 99%

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Dose‐dependent glycometabolic effects of sotagliflozin on type 1 diabetes over 12 weeks: The inTandem4 trial

Baker

Wason

Banks

et al. 2019

Diabetes Obesity Metabolism

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Aims To assess the dose‐related effects of sotagliflozin, a novel dual inhibitor of sodium‐glucose co‐transporters‐1 and ‐2, in type 1 diabetes (T1D). Materials and methods In this 12‐week, multicentre, randomized, double‐blind, placebo‐controlled dose‐ranging trial, adults with T1D were randomized to once‐daily placebo (n = 36) or sotagliflozin 75 mg (n = 35), 200 mg (n = 35) or 400 mg (n = 35). Insulin was maintained at baseline doses. The primary endpoint was least squares mean (LSM) change in glycated haemoglobin (HbA1c) from baseline. Other endpoints included proportion of participants with ≥0.5% HbA1c reduction and assessments of 2‐hour postprandial glucose (PPG), weight, and urinary glucose excretion (UGE). Results From a mean baseline of 8.0% ± 0.8% (full study population), placebo‐adjusted LSM HbA1c decreased by 0.3% (P = .07), 0.5% (P < .001) and 0.4% (P = .006) with sotagliflozin 75 mg, 200 mg and 400 mg, respectively, at week 12. In the placebo and sotagliflozin 75 mg, 200 mg and 400 mg groups, 33.3%, 37.1%, 80.0% and 65.7% of participants achieved an HbA1c reduction ≥0.5%. Placebo‐adjusted PPG decreased by 22.2 mg/dL (P = .28), 28.7 mg/dL (P = .16) and 50.2 mg/dL (P = .013), UGE increased by 41.8 g/d (P = .006), 57.7 g/d (P < .001) and 70.5 g/d (P < .001), and weight decreased by 1.3 kg (P = .038), 2.4 kg (P < .001) and 2.6 kg (P < .001) with sotagliflozin 75 mg, 200 mg and 400 mg, respectively. One case of severe hypoglycaemia occurred in each sotagliflozin group and one case of diabetic ketoacidosis (DKA) occurred with sotagliflozin 400 mg. Conclusions Combined with stable insulin doses, sotagliflozin 200 mg and 400 mg improved glycaemic control and weight in adults with T1D. Sotagliflozin 400 mg reduced PPG levels. UGE increased with all sotagliflozin doses. Rates of severe hypoglycaemia and DKA were low (NCT02459899).

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Section: Discussionsupporting

confidence: 87%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dose‐dependent glycometabolic effects of sotagliflozin on type 1 diabetes over 12 weeks: The inTandem4 trial

Baker

Wason

Banks

et al. 2019

Diabetes Obesity Metabolism

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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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“…The STOP DKA Protocol has many recommendations that align with those in previously published DKA risk mitigation documents . One of the unique features of the STOP DKA Protocol is that it emphasizes a stepwise approach that takes its cue from the patient's glycaemia and ketone status.…”

Section: Use Of Sglt Inhibitors In Type 1 Diabetes and The Stop Dka Pmentioning

confidence: 99%

Sodium‐glucose co‐transporter inhibitors, their role in type 1 diabetes treatment and a risk mitigation strategy for preventing diabetic ketoacidosis: The STOP DKA Protocol

Goldenberg

Gilbert

Hramiak

et al. 2019

Diabetes Obesity Metabolism

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Recent phase 3 clinical trials have evaluated the impact of adding sodium‐glucose co‐transporter (SGLT) inhibitors to the type 1 diabetes armamentarium. These trials studied SGLT2 inhibitors (dapagliflozin and empagliflozin) and a dual SGLT1 and SGLT2 inhibitor (sotagliflozin), and demonstrated that these oral non‐insulin antihyperglycaemic medications are able not only to improve glycaemic control, but also to reduce body weight and extend time in range without increasing rates of hypoglycaemia in type 1 diabetes. Diabetic ketoacidosis (DKA) is a feature of type 1 diabetes and the risk is increased when SGLT inhibitors are used in type 1 diabetes. To minimize the risk of DKA and still gain the multiple benefits, we developed the “STOP DKA Protocol “, an easily accessible and practical tool, that provides a risk mitigation strategy for reducing DKA in patients with type 1 diabetes being treated with SGLT inhibitors.

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HbA1c and Hypoglycemia Reductions at 24 and 52 Weeks With Sotagliflozin in Combination With Insulin in Adults With Type 1 Diabetes: The European inTandem2 Study

Abstract: In a 1-year study, sotagliflozin was associated with statistically significant HbA reductions. More episodes of DKA and fewer episodes of documented and severe hypoglycemia were observed in patients using sotagliflozin relative to those receiving placebo (ClinicalTrials.gov, NCT02421510).

Cited by 137 publications

References 33 publications

Dose‐dependent glycometabolic effects of sotagliflozin on type 1 diabetes over 12 weeks: The inTandem4 trial

Dose‐dependent glycometabolic effects of sotagliflozin on type 1 diabetes over 12 weeks: The inTandem4 trial

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

Sodium‐glucose co‐transporter inhibitors, their role in type 1 diabetes treatment and a risk mitigation strategy for preventing diabetic ketoacidosis: The STOP DKA Protocol

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