Sotagliflozin Added to Optimized Insulin Therapy Leads to Lower Rates of Clinically Relevant Hypoglycemic Events at Any HbA1c at 52 Weeks in Adults with Type 1 Diabetes

Danne, Thomas; Pettus, Jeremy; Giaccari, Andrea; Cariou, Bertrand; Rodbard, Helena W.; Weinzimer, Stuart A.; Bonnemaire, Mireille; Sawhney, Sangeeta; Stewart, John; Wang, Stella; Castro, Rita; Garg, Satish K.

doi:10.1089/dia.2019.0157

Cited by 20 publications

(19 citation statements)

References 31 publications

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“…In clinical trials, patients with type 1 diabetes who received sotagliflozin 200 or 400 mg added to insulin experienced significant improvements in glycemic control (including A1C, 2-h postprandial glucose, and time in range), and improved body weight, blood pressure, and patient-reported outcomes. Patients receiving sotagliflozin also had a significant reduction in the number of hypoglycemic (blood glucose ≤55 mg/dL) and severe hypoglycemic events (400-mg group only) ( 12 , 13 , 28 , 29 ). In these trials, the AE profile was generally consistent with that observed with SGLT2 inhibitors in type 2 diabetes trials, including an increased incidence of genital mycotic infections and DKA.…”

Section: Discussionmentioning

confidence: 96%

Diabetic Ketoacidosis and Related Events With Sotagliflozin Added to Insulin in Adults With Type 1 Diabetes: A Pooled Analysis of the inTandem 1 and 2 Studies

McGuire

Danne

Kushner³

et al. 2020

Diabetes Care

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OBJECTIVE To evaluate the incidence and risk factors for diabetic ketoacidosis (DKA) and related adverse events (AEs) in adults with type 1 diabetes treated with sotagliflozin adjunctive to insulin. RESEARCH DESIGN AND METHODS Data from two identically designed, 52-week, randomized studies were pooled and analyzed for DKA, changes in β-hydroxybutyrate (BHB), and percentage of patients with BHB >0.6 and >1.5 mmol/L. The patients were administered placebo, sotagliflozin 200 mg, or sotagliflozin 400 mg once daily. RESULTS A total of 191 ketosis-related AEs were reported, and 98 underwent adjudication. Of these, 37 events (36 patients) were adjudicated as DKA, with an exposure-adjusted incidence rate of 0.2, 3.1, and 4.2 events per 100 patient-years for placebo, sotagliflozin 200 mg, and sotagliflozin 400 mg, respectively. No patient died of a DKA event. From a baseline BHB of ∼0.13 mmol/L, sotagliflozin treatment led to a small median increase over 52 weeks (≤0.05 mmol/L at all time points). Of sotagliflozin-treated patients, approximately 47% and 7% had ≥1 BHB measurement >0.6 mmol/L and >1.5 mmol/L, respectively (vs. 20% and 2%, respectively, of placebo-treated patients). Subsequent to the implementation of a risk mitigation plan, annualized DKA incidence was lower versus preimplementation in both the sotagliflozin 200 and 400 mg groups. CONCLUSIONS In patients with type 1 diabetes, confirmed DKA incidence increased when sotagliflozin was added to insulin compared with insulin alone. A lower incidence of DKA was observed following the implementation of an enhanced risk mitigation plan, suggesting that this risk can be managed with patient education.

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Section: Discussionmentioning

confidence: 96%

Diabetic Ketoacidosis and Related Events With Sotagliflozin Added to Insulin in Adults With Type 1 Diabetes: A Pooled Analysis of the inTandem 1 and 2 Studies

McGuire

Danne

Kushner³

et al. 2020

Diabetes Care

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“…Vigersky also proposed a scoring system based on the combination of HbA1c with the risk of hypoglycemia (also using incidence of SH requiring assistance from others). 23,49 With the current widespread availability of CGM and the ability to measure %TBR using any desired threshold (including, but not limited to <54, 63, or <70 mg/dL), it is likely that the metric %TBR would usually be preferable to use of incidence of SH, 1,23,[41][42][43] provided that sufficient CGM data were available both in terms of quantity (duration) and accuracy. 45,46 The sensitivity when using %TBR can be considerably greater than when using incidence of severe hypoglycemia because of the much higher frequency of observations and corresponding better accuracy measuring event rates.…”

Section: Resultsmentioning

confidence: 99%

“…1) and the corresponding regression analysis can be used to evaluate whether the relationships for two forms of therapy or other kinds of interventions are equivalent, corresponding to a single smooth relationship. 1,41,42,48,52 The graphical approach shown in Figure 1 has been used to examine the curvilinear relationships between incidence of severe hypoglycemia and HbA1c to compare the properties of three insulin formulations, viz., Neutral Protamine Hagedorn (NPH), glargine U-100, and detemir insulin. 41 Graphical analysis (cf.…”

Section: Two-dimensional Graphical Analyses Of Efficacy and Safetymentioning

confidence: 99%

Quality of Glycemic Control: Assessment Using Relationships Between Metrics for Safety and Efficacy

Rodbard

2021

Diabetes Technology & Therapeutics

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Numerous methods have been proposed as measures of quality of glycemic control resulting in confusion regarding the best choice of metric to use by clinicians and researchers. Some methods use a single metric such as HbA1c, Mean Glucose, %Time In Range (%TIR), or Coefficient of Variation (%CV). Others use a combination of up to seven metrics, for example, Q-Score, Comprehensive Glucose Pentagon (CGP), and Personal Glycemic State (PGS). A recently proposed Composite continuous Glucose monitoring index utilizes three metrics: %TIR, Time Below Range (%TBR), and standard deviation (SD) of glucose. This review proposes that only two metrics can be sufficient when monitoring an individual patient or when comparing two or more forms of management interventions. These two metrics comprise (1) a measure of efficacy such as Mean Glucose, HbA1c, %TIR, or %Time Above Range (%TAR) and (2) a measure of safety based on risk of hypoglycemia such as %TBR, Low Blood Glucose Index (LBGI), or frequency of specified types of hypoglycemic events per patient year. By analysis of the two-dimensional graphical and statistical relationships between metrics for safety and efficacy and by testing identity versus nonidentity of these relationships, one can improve sensitivity for detection of the effects of medications and of other therapeutic interventions, avoid the need for arbitrary scoring systems for glucose values falling within versus outside the target range, and offer the advantage of conceptual and practical simplicity.

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“…Moreover, in Thomas Danne et al analysis, adding sotagliflozin to insulin therapy resulted in lower hypoglycemia events than the placebo group. Both 200 and 400mg of sotagliflozin were related to a substantially lower incidence of hypoglycemic attacks than placebo [17].…”

Section: Activity Of Sodium-glucose Co-transportermentioning

confidence: 85%

The Role of SGLT-2 Inhibitors as an Adjuvant to Insulin Therapy in Type-1 Diabetes Mellitus- Literature Review

Alshehri

Asiri

Algarni

et al. 2021

JPRI

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Background: Type 1 diabetes mellitus is the main risk factor for cardiovascular complications. Therefore, intensified insulin therapy might be needed to achieve better glycemic control in some patients. However, insulin therapy might lead to increase body weight and induce hypoglycemia. Increase body weight is directly correlated to insulin resistance, the main factor for cardiovascular risk. Objective: To assess the effectiveness of adding SGLT2 inhibitors to insulin therapy in type 1 diabetes mellitus. Methods: We searched in the PubMed database looking for relevant articles on the topic. We used Mesh words search, including SGLT2 inhibitor, sotagliflozin, type 1 diabetes mellitus, insulin treatment. Conclusion: Adding oral antidiabetic agents, such as SGLT2 or dual SGLT inhibitors to insulin regimen might be beneficial in improving insulin resistance. Thus, it achieved better insulin resistance by decrease daily insulin requirements and bodyweight control, leading to better cardiovascular outcomes among Type-1 diabetes patients.

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Sotagliflozin Added to Optimized Insulin Therapy Leads to Lower Rates of Clinically Relevant Hypoglycemic Events at Any HbA1c at 52 Weeks in Adults with Type 1 Diabetes

Cited by 20 publications

References 31 publications

Diabetic Ketoacidosis and Related Events With Sotagliflozin Added to Insulin in Adults With Type 1 Diabetes: A Pooled Analysis of the inTandem 1 and 2 Studies

Diabetic Ketoacidosis and Related Events With Sotagliflozin Added to Insulin in Adults With Type 1 Diabetes: A Pooled Analysis of the inTandem 1 and 2 Studies

Quality of Glycemic Control: Assessment Using Relationships Between Metrics for Safety and Efficacy

The Role of SGLT-2 Inhibitors as an Adjuvant to Insulin Therapy in Type-1 Diabetes Mellitus- Literature Review

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