Effect of Subetta on glycemic control in patients with type 2 diabetes mellitus: results of a multicenter, double-blind, placebo-controlled, randomized clinical study

Background. Oral antidiabetic drugs (OADs) are the mainstay of drug therapy for type 2 diabetes mellitus (DM2), their choice depends on the dominant clinical problem and individual goals. However, despite the significant replenishment of doctors’ arsenal with modern drugs, not all patients manage to achieve optimal glycemic control and maintain it for a long time. If the OADs are ineffective, treatment is supplemented with insulin administration. One of the possible methods of achieving the individual goal of DM2 therapy is the use of the drug Subetta. Objective. Evaluation of the efficacy and safety of Subetta for patients without optimal control of DM2 during treatment with basal insulin in combination with metformin and/or sulfonylurea medication. Methods. A multicenter, double-blind, placebo-controlled, randomized clinical trial was conducted in 17 medical centers in the Russian Federation. The effectiveness of therapy was analyzed on the basis of data from 140 randomized patients in whom glycated hemoglobin (HbA1c) level remained within 7.0-10.0% during complex therapy (basal insulin ≥10 U/day+metformin and/or sulfonylurea medication) for ≥3 months prior to study enrollment. Patients in the Subetta group (n=73), in addition to complex therapy, received the tested drug, 1 tablet 4 times a day for 36 weeks, patients in the placebo group (n=67) - complex therapy plus placebo according to the Subetta regimen. The primary endpoint was the change in mean HbA1c level at 12, 24 and 36 weeks of treatment from baseline. The dynamics of fasting plasma glucose (FPG) level, indicators of the 7-point self-monitoring of blood glucose (SMBG) profile, daily doses of insulin and OADs, body weight and body mass index (BMI) during 36 weeks of treatment were assessed as secondary endpoints. Results. Patients in both groups did not differ in demographic, anthropometric and baseline clinical characteristics. According to Intention-to-Treat analysis, the mean decrease in HbA1 level in patients of the Subetta group after 12, 24 and 36 weeks of treatment was -0.53±1.06%, -0.54±1.00% and -0.54±1.11%, which was significantly different compared to the placebo group (-0.01±1.06%, -0.07±1.19% and +0.15±1.07%; p=0.0096, p=0.0107 and p=0.0009, respectively). The target HbA1c values at 36 weeks were reached by 19.2% of patients in the Subetta group (versus 4.5% in the placebo group; p=0.009). The results of the per protocol analysis showed an even more significant decrease in HbA1c level compared with placebo therapy: -0.70±1.04%, -0.65±1.04% and -0.70±1.13% versus +0.03±1.09%, -0.07±1.21%, and +0.15±1.07% (p=0.0006, p=0.0056 and p=0.0003, respectively). FPG level after 4 weeks of Subetta’s use decreased by -0.5±2.6 mmol/L (versus -0.1±3.2 mmol/L in the placebo group; p=0.3362) and remained at a stable level in the next 24 weeks. In the placebo group, the FPG level, on the contrary, increased: +0.9±4.1 mmol/L after 24 weeks (p=0.2778) and + 1.0±3.7 mmol/L after 36 weeks (p=0.2778). After 36 weeks of treatment with Subetta, there was a tendency towards a decrease in postprandial glycemia (according to the 7-point SMBG profile), basal insulin doses (-0.9±2.4 IU/day versus +3.5±9.5 IU/day in placebo group; p=0.0605) and BMI (-0.04±0.78 kg/m2 versus +0.14±1.33 kg/m2 in the placebo group; p=0.3410). There were 2 episodes of symptomatic daytime hypoglycemia in the Subetta group and 8 in the placebo group. No cases of evere hypoglycemia were identified. Subetta did not adversely affect the vital signs of the study participants. A total of 49 adverse events (AEs) were noted in 23 (30.3%) patients in the Subetta group and 39 AEs in 25 (34.7%) participants in the placebo group. The number of patients with AEs, as well as AEs related to one or another MedDRA code (Medical Dictionary of Regulatory Activity Terminology), did not differ between the two groups (p=0.60). The distribution of AEs depending on the severity (p=0.419) and the reliability of the causal relationship with the drug (p=0.166) did not differ between two groups. No AEs were reported that were reliably associated with the tested drug. Biochemical blood test, general clinical blood and urine tests did not reveal clinically significant deviations and differences in both groups after 12, 24 and 36 weeks of treatment. Compliance rates were close to 100% in the two groups. Conclusion. The combination of Subetta with basal insulin and OADs (metformin and/or sulfonylurea medication) is a rational combination for DM2. In patients without control of DM2 against the background of basal insulin and OAds for ≥3 months, the inclusion of Subetta leads to a significant optimization of glycemic control. The HbA1c level achieved in 12 weeks remains stable over the next 24 weeks of treatment. The therapeutic efficacy of the drug is combined with a good safety profile and a high level of patient adherence to therapy.

type 2 diabetes mellitus, basal insulin, metformin, sulfonylureas, glycemic control, Subetta