Effects of Sotagliflozin Added to Insulin in Patients with Type 1 Diabetes

Garg, Satish K.; Henry, Robert R.; Banks, Phillip; Buse, John B.; Davies, Melanie J.; Fulcher, Gregory; Pozzilli, Paolo; Gesty‐Palmer, Diane; Lapuerta, Pablo; Simó, Rafael; Danne, Thomas; McGuire, Darren K.; Kushner, Jake A.; Peters, Anne L.; Strumph, Paul

doi:10.1056/nejmoa1708337

Cited by 346 publications

(400 citation statements)

References 34 publications

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“…In the sotagliflozin group, 28.6% of patients met the primary end point versus 15.2% of patients in the placebo group. Moreover, the patients in the sotagliflozin group achieved a significantly lower HbA1c, systolic blood pressure and body weight and required significantly less daily insulin compared to the placebo group [18]. The efficacy results of these three main trials are summarized in Table 2.…”

Section: Use Of Sglt2 Inhibitors In Type 1 Diabetic Patients: Effectsmentioning

confidence: 99%

“…As stated previously, intestinal SGLT1 inhibition can cause diarrhea. The inTandem trial showed that twice as many patients reporting diarrhea were in the sotagliflozin group compared to the placebo group [18]; however, overall this risk seemed lower than expected indicating a potential therapeutic window. After reabsorption into the systemic circulation, sotagliflozin will inhibit SGLT2 in the kidney.…”

Section: Use Of Sglt2 Inhibitors In Type 1 Diabetic Patients: Effectsmentioning

confidence: 99%

“…Volume depletion is a risk factor for DKA. Adjudication was done in this trial to confirm reported DKA events by a committee blinded to the treatment arm [18]. “Serious DKA” was defined in all 3 trials by any DKA case that required hospitalization [16–18].…”

Section: Use Of Sglt2 Inhibitors In Type 1 Diabetic Patients: Safetymentioning

confidence: 99%

“…Adjudication was done in this trial to confirm reported DKA events by a committee blinded to the treatment arm [18]. “Serious DKA” was defined in all 3 trials by any DKA case that required hospitalization [16–18]. In summary, two of the three trials showed an increased risk in serious DKA with SGLT2 inhibitors in type 1 diabetic patients compared to placebo.…”

Section: Use Of Sglt2 Inhibitors In Type 1 Diabetic Patients: Safetymentioning

confidence: 99%

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The Potential Role of SGLT2 Inhibitors in the Treatment of Type 1 Diabetes Mellitus

Fattah

Vallon

2018

Drugs

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Type 1 diabetes mellitus is a difficult disease to treat due to the relative paucity of therapeutic options other than injectable insulin. The latter, however, can induce hypoglycemia, which has been linked to enhanced cardiovascular risk. Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of oral anti-hyperglycemic medications that do not increase the hypoglycemia risk and are US Food and Drug Administration (FDA) approved in type 2 diabetes mellitus. SGLT2 inhibitors may also be of benefit in type 1 diabetic patients, in addition to insulin, although they have not yet been approved for this indication. By blocking SGLT2 in the early proximal tubules of the kidney, these drugs decrease renal glucose retention, which is enhanced in hyperglycemia, thereby improving blood glucose control, in type 1 and type 2 diabetic patents. Their low hypoglycemia risk is due to the compensating reabsorption capacity of another glucose transporter, SGLT1, in the downstream late proximal tubule and the body's metabolic counter-regulation, which remains intact during SGLT2 inhibition. When insulin dosage is lowered too much, SGLT2 inhibitors can enhance ketogenesis to the extent that the risk of diabetic ketoacidosis increases, particularly in type 1 diabetic patients. SGLT2 inhibitors improve the renal and cardiovascular outcome in type 2 diabetic patients. The mechanisms likely include a reduction in glomerular hyperfiltration, blood pressure, volume overload, and body weight, as well as lowering blood glucose without increasing the hypoglycemia risk. The same mechanistic effects are induced in type 1 diabetic patients. More studies are needed with SGLT2 inhibitors in type 1 diabetic patients, including renal and cardiovascular clinical outcome trials, to fully evaluate their therapeutic potential in this specific population.

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Section: Use Of Sglt2 Inhibitors In Type 1 Diabetic Patients: Effectsmentioning

confidence: 99%

Section: Use Of Sglt2 Inhibitors In Type 1 Diabetic Patients: Effectsmentioning

confidence: 99%

Section: Use Of Sglt2 Inhibitors In Type 1 Diabetic Patients: Safetymentioning

confidence: 99%

Section: Use Of Sglt2 Inhibitors In Type 1 Diabetic Patients: Safetymentioning

confidence: 99%

See 2 more Smart Citations

The Potential Role of SGLT2 Inhibitors in the Treatment of Type 1 Diabetes Mellitus

Fattah

Vallon

2018

Drugs

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“…In the inTANDEM study, addition of sotagliflozin (400 mg) for 24 weeks reduced HbA1c (p<0.0001); the incidence of severe hypoglycaemia was similar in the treated (3%) and placebo (2.4%) groups and diabetic ketoacidosis occurred in 3% of patients receiving sotagliflozin and 0.4% of patients in the placebo group. 27,28 Anything else? The Messe Berlin (aka Berlin ExpoCenter City), Messedamm 22, will host EASD 2018.…”

Section: … Newer Agentsmentioning

confidence: 99%

Impressions from EASD 2017

Day

2017

Br J Diabetes

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Sodium Glucose Cotransporter Inhibitors for the Treatment of Diabetes

Jesus

Harrison²,

Dore

2021

Burger's Medicinal Chemistry and Drug Discovery

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Worldwide, the incidence of diabetes mellitus, a chronic metabolic disease that results in four million deaths from it and associated complications annually, is increasing and its treatment is an enormous public health concern. Type 1 diabetes is treated by insulin, but a variety of drugs are used to treat the more prevalent type 2 diabetes. Inhibitors of sodium glucose cotransporters (SGLTs) are the newest drugs to reach the market to achieve the blood‐glucose control needed to treat type 2 diabetes. SGLT1 and 2 carry out renal reabsorption of more than 90% of glucose from urine against a concentration gradient using the electrochemical energy from the cotransport of sodium ions. Blocking SGLTs causes excess glucose to be excreted through the urine, reducing blood sugar. The first known SGLT inhibitor was the O ‐glycosylated flavonoid natural product phlorizin, which enabled the discovery of SGLTs and served as the initial lead compound for medicinal chemistry. O ‐ and C ‐Glycosylated flavonoid and dihydrochalcone natural products also inhibit SGLTs. The drugs on the market today, dapagliflozin, canagliflozin, empagliflozin, ertugliflozin, and others, are all aryl C ‐glycosides. They are selective for SGLT2 over SGLT1 to avoid adverse side effects associated with SGLT1 inhibition. Studies have suggested that SGLT inhibitors have a renal and cardiovascular protective effect that is advantageous, although their use increases the risk of urinary tract and genital infections and ketoacidosis. SGLT inhibitors are in trials as an adjuvant to insulin for the treatment of type 1 diabetes.

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Effects of Sotagliflozin Added to Insulin in Patients with Type 1 Diabetes

Cited by 346 publications

References 34 publications

The Potential Role of SGLT2 Inhibitors in the Treatment of Type 1 Diabetes Mellitus

The Potential Role of SGLT2 Inhibitors in the Treatment of Type 1 Diabetes Mellitus

Impressions from EASD 2017

Sodium Glucose Cotransporter Inhibitors for the Treatment of Diabetes

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