Lisa Neuman

Two pivotal studies on sotagliflozin were presented at the American Diabetes Association (ADA)’s 77th Scientific Sessions in San Diego.  

The studies, inTandem1 and inTandem2, yielded 24-week data that demonstrated some key efficacy and safety results for the use of sotagliflozin (Lexicon Pharmaceuticals, Inc.) in patients with type 1 diabetes (T1D). As a first-in-class, sotagliflozin is an oral dual inhibitor of sodium-glucose co-transporter types 1 and 2 (SGLT-1 and SGLT-2), proteins that are responsible for glucose regulation. SGLT-1 absorbs glucose in the gastrointestinal tract, and SGLT-2 reabsorbs it in the kidneys.  

inTandem1 and inTandem2 both showed that when used on top of optimized insulin, sotagliflozin 200 mg and 400 mg both reduced hemoglobin A1C compared with placebo (P < .001 in both studies).   The drug was generally well tolerated, with a low rate of severe hypoglycemia seen in both studies. Across both studies, severe hypoglycemia occurred less frequently on the sotagliflozin regiment than it did on placebo in 3 of 4 arms.  

Also in both studies, the rate of diabetic ketoacidosis was low (0.4% to 3.1% over the 24 weeks); it was higher in patients who were on an insulin pump than it was in patients taking multiple-dose injections.   The inTandem1 study—presented with the title, Twenty-Four Week Efficacy and Safety of Sotagliflozin, a Dual SGLT1 and SGLT2 Inhibitor, as Adjunct Therapy to Insulin in Type 1 Diabetes, at the ADA meeting&mdash;met its primary endpoint of change in A1C levels from baseline after the 24-week treatment period. Changes in A1C were 0.08% for placebo, 0.43% for the 200-mg dose, and 0.49% for the 400-mg dose. For patients treated with the 200-mg dose and the 400-mg dose, the differences compared with placebo were 0.36% and 0.41%, respectively (P < .001 for both doses).  

Secondary endpoints were also met in the 400-mg arm, with net benefit (defined as A1C <7.0% without an episode of severe hypoglycemia or diabetic ketoacidosis) weight, bolus insulin, fasting plasma glucose, as well as 2 patient-reported outcomes all being statistically significant. The secondary endpoints of net benefit and weight were also statistically significant in the 200-mg arm.  

The medication was generally well tolerated, with treatment emergent adverse events (AEs) occurring at rates of 67.5% for placebo, 67.3% for the 200-mg dose, and 71.0% for the 400-mg dose. Serious AEs occurred at rates of 3.4% for placebo, 3.8% for the 200-mg dose, and 6.9% for the 400-mg dose. Study discontinuation rates because of AEs were 1.5% for placebo, 1.1% for the 200-mg dose, and 3.8% for the 400-mg dose. No deaths were reported in the study.  

inTandem2 was presented at the ADA meeting with the title, Twenty-Four Week Efficacy and Safety of Sotagliflozin, a Dual SGLT1 and SGLT2 Inhibitor, as Adjunct Therapt to Insulin in Type 1 Diabetes. It yielded a reduction in A1C from baseline to 24 weeks of 0.03% for placebo (P = 0.54), 0.39% for the 200-mg dose (P < .001), and 0.37% for the 400-mg dose (P < .001). The mean difference for the 200-mg and 400-mg doses compared with placebo were 0.36% and 0.35%, respectively (P < .001 for both doses).  

Also compared to placebo, both doses were statistically significant (P < .001) on the net benefit endpoint, A1C <7.0% without an episode of severe hypoglycemia or diabetic ketoacidosis.   Like inTandem1, the medication was generally well tolerated, with incidence rates of treatment emergent AEs being 51.4% for placebo, 55.9% for the 200-mg dose, and 54.4% for the 400-mg dose. The incidence rate for serious AEs was 3.5% for the placebo and 4.2% for both the 200-mg and 400-mg doses.  

The discontinuation rates because of AEs were 1.6% for the placebo, 1.9% for the 200-mg dose, and 3.0% for the 400-mg dose. Two deaths were reported in the placebo arm; no deaths were reported in either the 200-mg or 400-mg dose arms.  

"There remains a need for oral therapeutic agents in addition to insulin to help improve quality of life in patients with type 1 diabetes by reducing the diabetes management burden and sotagliflozin has that potential," John Buse, MD, PhD, lead investigator of inTandem1 and professor of medicine, chief of the Division of Endocrinology and Metabolism, director of the Diabetes Care Center, and executive associate dean for clinical research at the University of North Carolina School of Medicine, said in a news release announcing the results. "Sotagliflozin has demonstrated, in three Phase 3 studies, the ability for patients to achieve glycemic goals with a safety profile that supports its utility in the type 1 diabetes community."  

"We are extremely pleased with the results achieved by sotagliflozin in its three Phase 3 studies," Lonnel Coats, Lexicon's president and chief executive officer, said in the same news release. "We look forward to seeing the pooled continuous glucose monitoring data from inTandem1 and inTandem2 as well as data from secondary endpoints in inTandem2 in the third quarter."

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Sotagliflozin effective in treating patients with type 1 diabetes.

Findings from inTandem1 and inTandem2 Featured at ADA Scientific Sessions

A new analysis has shown that insulin glargine 100 Units/mL and lixisenatide 33 mcg/mL in combination lowered hemoglobin A1C levels by 1.09% to 2.41% after 30 weeks of treatment in a population of adult patients with type 2 diabetes (T2D) who had been previously treated with 15 to 40 units of basal insulin daily.

The research was presented yesterday in a poster session at the American Diabetes Association (ADA)’s 77th Scientific Sessions, which are being held in San Diego June 8 to 13.

Among the post-hoc analysis of data from the LixiLan-L Phase 3 study were that all subgroups treated with the insulin glargine/lixisenatide combination (Soliqua/Sanofi) achieved a mean A1C below 7% after the 30-week treatment period. The trial grouped the participants by A1C level at screening.

“Lowering elevated HbA1c is an important treatment goal in people with diabetes,” Riccardo Perfetti, vice president, head of Global Medical Affairs Diabetes for Sanofi, said in a news release distributed after the presentation. “This analysis demonstrated the substantial blood sugar lowering effect that can be achieved with Soliqua 100/33, and also its potential to help adults reach HbA1c levels below 7%, which is recommended as a treatment goal by bodies such as the American Diabetes Association for many adults with diabetes.”

The ADA, in a supplement to its January 2017 issue of 

, published recommendations that “A reasonable A1C goal for many nonpregnant adults is <7% (53 mmol/mol).”

The LixiLan-L trial compared the effectiveness of the combination of insulin glargine 100 Units/mL and lixisenatide 33 mcg/mL with insulin glargine 100 Units/mL alone in 736 adult patients with T2D that was not adequately controlled at screening. These patients were on a regimen of 15 to 40 units of basal insulin daily, alone or combined with 1 or 2 oral antidiabetic agents.

The primary outcome of the LixiLan-Lstudy, a statistically significant reduction in A1C compared with insulin glargine 100 Units/mL, was previously reported by Sanofi in September 2015.

Lixisenatide is a glucagon-like peptide-1 (GLP-1) receptor agonist. These drugs work in the same pathway as dipeptidyl peptidase 4 (DPP-4) inhibitors, a class of oral hypoglycemic drugs, but because GLP-1 receptor agonists are peptide-based therapies, they, like insulin, require subcutaneous injection to avoid being degraded by the enzymes in the gastrointestinal tract.

 One of the advantages of GLP-1 receptor agonists is that they, like the DPP-4 inhibitors, also have a lower risk of causing hypoglycemia but are more potent than the DPP-4 inhibitors.

For this study, patients were split in 3 categories based on A1C at screening: ≤8%, >8% to ≤9%, and >9%, and data were evaluated for the 660 patients who completed the 30-week study period. The Least Squares mean reduction in A1C for the insulin glargine 100 Units/mL and lixisenatide 33 mcg/mL treatment group were 1.09%, 1.44%, and 2.41%, respectively, after 30 weeks. The mean A1C observed for each subgroup was 

7% with insulin glargine 100 Units/mL and lixisenatide 33 mcg/mL alone (7.22%, 7.42%, and 7.66%, respectively), and reductions in A1C were also greater in this group across all defined categories versus insulin glargine 100 Units/mL alone (

Findings presented at ADA conference highlight effiacy of insulin glargine/lixisenatide combination.

Soliqua Shows Promise Lowering Hemoglobin A1C Levels in Type 2 Diabetes

The results of the DELIVER 3 retrospective observational study have been presented at the American Diabetes Association (ADA)’s 77

 Scientific Sessions in San Diego, California.

In making the presentation, Sanofi announced its new evidence demonstrating a significantly lower risk of hypoglycemia with similar blood sugar control in an at-risk population of senior adult patients (aged ≥65 years) with type 2 diabetes (T2D) after switching to Toujeo (insulin glargine 300 Units/mL) compared with switching to another basal insulin, including Lantus/Sanofi (insulin glargine 100 Units/mL), Levemir/Novo Nordisk (insulin detemir) and Tresiba/Novo Nordisk (insulin degludec).

Hypoglycemia was identified in the dataset by 

 diagnosis codes or by plasma glucose, measured as ≤ 70 mg/dL by laboratory test.

A long-acting insulin used to control blood sugar in adult patients with diabetes, insulin glargine 300 Units/mL contains 3 times as much insulin in 1 mL as standard insulin 100 Units/mL. It should not be used to treat diabetic ketoacidosis, and should not be used in children with diabetes.

"Older patients with type 2 diabetes are disproportionately impacted by hypoglycemia and its consequences," Jeremy Pettus, an assistant professor in the Division of Endocrinology at the University of California San Diego, said in a company news release announcing the results. "Observational real-world data such as DELIVER 3 can contribute to clinical decision-making, helping physicians to better advise their patients in this important at-risk population."

The study found that the patients who switched to insulin glargine 300 Units/mL were 57% less likely to experience hypoglycemia at the 6-month follow-up (Odds Ratio: 0.432, 95% CI: 0.307 to 0.607, 

 < .0001) than the patients who switched to another basal insulin with similar glycemic control (least squares mean difference —0.09%, 

The DELIVER 3 findings are consistent with the evidence from DELIVER 2, another retrospective observational study that included 2 matched cohorts of 1827 (N = 3,654) adult patients with T2D who were using basal insulin and switched to either insulin glargine 300 Units/mL or another basal insulin. DELIVER 2 showed 33% fewer hypoglycemic events in a broader population of adult patients with T2D 6 months after switching. The company estimates that this would result in an all-cause healthcare cost savings of up to approximately $2,000 per patient, per year.

Riccardo Perfetti, head of the Global Diabetes Medical Team for &lrm;Sanofi, stated in the news release that, combined, the findings from DELIVER 2 and DELIVER 3 "demonstrate the real-life clinical benefit of Toujeo versus other basal insulins, and how this translates into overall cost savings.”

He went on to explain the company’s next steps, saying, “Complementing these observational studies in a real-life setting, Sanofi is also conducting a unique program of 3 randomized, prospective, open-label, real-life clinical studies with Toujeo. The methodology of these studies could provide a better understanding of the comparative benefit…versus other basal insulins, and the findings might be relevant to future clinical practice and evaluation of overall cost of care."

The 3 randomized, prospective, real-life clinical studies, called ACHIEVE CONTROL, REACH CONTROL, and REGAIN CONTROL, include more than 4500 people with T2D in the United States and Europe. These patients are either starting basal insulin treatment or switching from another basal insulin treatment. The initial results are anticipated later in 2017.

Patients who switched to insulin glargine were 57% less likely to experience hypoglycemia.

Study Shows Switching to Toujeo Lowers Risk of Hypoglycemia in Seniors With Diabetes

The results of a randomized, double-blind, placebo-controlled study being presented at the American Academy of Neurology’s 69th Annual Meeting in Boston April 22-28, 2017, suggests that cannabidiol may cut the number of seizures in half for some children and adults who have Lennox-Gastaut syndrome (LGS).  

LGS begins in childhood and is a severe form of epilepsy. Those with the syndrome can experience different types of seizures, including atonic drop seizures, in which there is a sudden loss of muscle tone, causing the individual to go limp or collapse. They can also experience tonic-clonic seizures, in which they lose consciousness, their muscles stiffen, and they go into full-body convulsions. People with LGS usually have some level of intellectual development impairment.  

Cannabidiol is a cannabis compound that does not possess the psychoactive properties of THC, and therefore does not create a “high” or a feeling of being “stoned.” According to a news release ahead of the conference, in the study, nearly 40% of the patients with LGS had at least a 50% reduction in drop seizures when they took a liquid form of cannabidiol, compared with 15% of patients who took a placebo.  

“Our study found that cannabidiol shows great promise in that it may reduce seizures that are otherwise difficult to control,” said study author Anup Patel, MD, of Nationwide Children’s Hospital and The Ohio State University College of Medicine in Columbus, and a member of the American Academy of Neurology.  

The study followed 225 patients with LGS for 14 weeks. Their average age was 16 years. The patients had an average of 85 drop seizures per month, had already tried an average of 6 epilepsy drugs that did not work and were taking an average of 3 epilepsy drugs during the study.  

Patients were given either a higher dose of 20 mg/kg daily cannabidiol, a lower dose of 10 mg/kg daily cannabidiol, or a placebo as an add-on to their current medications. Patients taking the 20-mg dose had a 42% reduction in drop seizures. Patients taking the 10-mg dose had a 37% reduction in drop seizures. Patients taking the placebo had a 17% reduction in drop seizures.  

Up to 66% of the patients who received cannabidiol reported improvement compared with 44% of the patients who received the placebo.    The two most common side effects reported were decreased appetite and sleepiness.  

“Our results suggest that cannabidiol may be effective for those with Lennox-Gastaut syndrome in treating drop seizures,” said Patel. “This is important because this kind of epilepsy is incredibly difficult to treat. While there were more side effects for those taking cannabidiol, they were mostly well-tolerated. I believe that it may become an important new treatment option for these patients.”  

A New Drug Application will be submitted to the FDA later this year. The study was supported by GW Pharmaceuticals, developer of cannabidiol. In the United States, GW operates as Greenwich Biosciences Inc.  

Lennox-Gastaut syndrome is a severe form of epilepsy that begins in childhood.