With Sanofi’s LixiLan® filed for FDA approval, GLP-1 agonist/basal insulin combinations could be potential game changers.
Sanofi’s LixiLan combines their insulin glargine Lantus Along with their GLP-1 Lyxumia (lixisenatide). Combining insulin Along with a GLP-1 agonist outcomes in reduced risk of hypoglycemia and, potentially, much better weight control. The FDA decision is expected in August; if approved, LixiLan will certainly enter the U.S. market ahead of competitor combo drug, Novo Nordisk’s Xultophy. Xultophy, which combines the GLP-1 Victoza Along with long-acting insulin Tresiba, is approved in Europe, yet not yet in the U.S.
Lixisenatide combined Along with glargine functions on the two the postprandial plasma glucose and fasting plasma glucose respectively, which reduces the HbA1c of type 2 diabetes patients. In previous studies, it was located that patients Along with raised HbA1c after initiation of insulin glargine had a tremendous reduction in HbA1c goals. Patients likewise showed an overall improvement in their postprandial hyperglycemia.
The goal of this study was to evaluate the efficacy and safety of lixisenatide in patients Along with HbA1c still raised after initiation of insulin glargine. Eligible participants were adult patients Along with type 2 diabetes. Using a double blind, parallel group randomized a population of (n=446) Along with HbA1c 7-10% despite oral therapy. Insulin glargine was periodically titrated throughout a 12-week run in. Candidates Along with fasting glucose ≤ 140mg/dl.(7.8 mmol/L) and HbA1c 7-9% were after that randomized to lixisenatide 20µg or placebo for 24 weeks while insulin titration continued. Injections were self-administered by participants. The primary outcome of measure that used ANCOVA model had a definite modification of HbA1c from baseline to week 24. Secondary efficacy of measure, however, included a modification from baseline to week 24 in 2-h PPG and blood glucose excursions throughout a standardized breakfast meal test; seven – point plasma – calibrated SMPG; FPG; physique weight; and standard day-to-day insulin glargine dosage. Measurements of physique weight, insulin dosage, FPG, and HbA1c were recorded at baseline, at endpoint, and at intervals throughout the trial. Additional categorical secondary efficacy variables included the percentage of participants accomplishing HbA1c target of < 7% or ≤6.5% at week 24.
With a energy of 90%, a difference of 0.4% modification of HbA1c was detected from baseline to week 24 between lixisenatide and placebo Along with the assumption that the common SD was 1.3% and a two-sided test at a 5% significance level. Safety variables were assessed in the safety population.
During the 12-week run-in phase the response to HbA1c decreased from baseline was drastically greater Along with lixisenatide compared Along with placebo having adjusted mean square (LS) adjustments of -0.7 and -0.4% respectively and LS mean difference for lixisenatide versus placebo was -0.3% (P<0.0001). The fasting plasma glucose did not modification much, yet the standardized meal study the LS mean difference of a 2-hr postprandial value from baseline between lixisenatide and placebo treatment was 57mg/dl.(-3.2 mmol/L) (95% CI, -4.0 to -2.4: P< 0.0001). SMPG had a substantial decrease Along with lixisenatide compared to the placebo (LS mean difference -0.4 mmol/L; P=0.0071). physique weight increased by 0.3kg in the lixisenatide group as compared to 1.2kg in the placebo group. Insulin dose, however, increased in the two teams Along with placebo being slightly greater compared to lixisenatide. Symptomatic hypoglycemia ensued in 20% of participants as compared to 11.7% in the placebo group. Severe side reactions adore injection site reaction, MI myeloma pancreatitis, enhance in calcitonin ensued in the two teams Along with no report of enhance in blood stress or heart rate.
In summary, for individuals that still have actually an HbA1c of 7.0% or greater even after the initiation of insulin glargine, the addition of lixisenatide to treatment program decreased their HbA1c and PPG drastically. However, future studies adore examining the tolerability and effectiveness of lixisenatide relative to various other therapies especially DPP-4 inhibitors, GLP-IRA agents inhibitors once added to basal insulin would certainly be fascinating. This study, however, had a variety of weaknesses, the very first being that Sanofi the manufacturer of lixisenatide funded it so there could be some bias. various other weaknesses included the study not addressing pertinent clinical questions adore exactly what added measures may enhance 40% of the participants randomized to lixisenatide that did not attain the 7.0% HbA1c goal. likewise the 12-week initiation and optimization of insulin glargine was also short. Finally, lixisenatide was assessed versus placebo quite compared to an energetic comparator.
LixiLan has actually likewise looked promising in phase 2 trials: in one recent study, the drug led to an standard A1c reduction of 1.8% (slightly better compared to the 1.6% seen Along with Lantus alone) along Along with reductions in post-meal blood sugars, no enhance in hypoglycemia, and reduced rates of gastrointestinal adverse effects.
Practice Pearls:
- The effect of lixisenatide treatment was many apparent after the morning meal.
- Adding lixisenatide prevented weight get Along with limited enhance in hypoglycemia and low A1c 1.8%.
- This treatment program must be an excellent alternative to patients not reaching their HbA1c targets Along with a recent initiation of basal insulin.
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Riddle, Mattew C.et al. “Including When – day-to-day Lixisenatide for Type 2 Diabetes Inadequately Controlled Along with Newly Initiated and Constantly Titrated Basal Insulin Glargine: A 24- week, Randomized, Placebo-Controlled Study (GetGoal Duo 1).” Diabetes Care 36.9 (2013): 2497- 2503. PMC. Web. 4 June 2016.
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