Efficacy and Safety of a Biosimilar Liraglutide (Melitide®) Versus the Reference Liraglutide (Victoza®) in People with Type 2 Diabetes Mellitus: A Randomized, Double-Blind, Noninferiority Clinical Trial.

INTRODUCTION: Liraglutide effectively controls blood glucose level and reduces body weight. The aim of this study was to compare the efficacy and safety of a biosimilar liraglutide (Melitide®; CinnaGen, Tehran, Iran) to the reference liraglutide (Victoza®; Novo Nordisk, Bagsvaerd, Denmark) in people with type 2 diabetes mellitus (T2DM). METHODS: In this phase 3 clinical noninferiority trial, adult patients with inadequately controlled T2DM and with hemoglobin A1C (HbA1C) levels of 7-10.5% on at least two oral glucose-lowering drugs with stable doses for at least 3 months were randomized to receive Melitide® (n = 150) or Victoza® (n = 150) 1.8 mg/day for 26 weeks. The primary outcome was assessment of the noninferiority of Melitide® to Victoza® in terms of change in HbA1C level with a prespecified margin of 0.4%. The secondary outcomes were the assessment of additional efficacy parameters (including the proportion of patients achieving HbA1C levels of < 7%), the incidence of adverse events, and immunogenicity. RESULTS: Of the 300 participants enrolled in this study, 235 were included in the per-protocol analysis (112 in the Melitide® group and 123 in the Victoza® group). The mean (standard deviation) changes in HbA1C were - 1.76% (1.22) in the Melitide® group and - 1.59% (1.31) in the Victoza® group. The upper limit of the 95% one-sided confidence interval (CI) of the mean difference between Melitide® and Victoza® in lowering HbA1C was lower than the predefined margin (mean difference - 0.18, 95% CI - 0.5 to 0.15). Similar findings were obtained with the intention-to-treat analysis. No statistically significant differences were observed between the two study arms regarding the proportion of patients achieving HbA1C < 7% (p = 0.210), other efficacy parameters (p > 0.05), and reported adverse events (p = 0.916). Furthermore, none of the patients developed anti-liraglutide antibodies. CONCLUSION: The biosimilar liraglutide (Melitide®) was noninferior in efficacy and comparable in safety when compared with the reference liraglutide. TRIAL REGISTRATION: NCT03421119.

Healthcare System Responsiveness in Covid-19: An Experience from Capital City of I.R of Iran.

Background: As a public health emergency, coronavirus disease 2019 (Covid-19) is a threat to our future; therefore, appropriate health system responsiveness (HSR), as an important criterion, is of crucial importance. This study aimed to evaluate the different dimensions of responsiveness of healthcare centers, both public and private, providing COVID-19 services in Tehran. Methods: Following a cross-sectional design, this study was conducted in Tehran (the capital city of I.R. Iran) from May to November 2020. Data were collected using the World Health Organization (WHO) questionnaire on responsiveness. Two hundred questionnaires were filled out through face-to-face or phone call interviews in two public and private hospitals (100 in each) providing Covid-19 services. Participants were selected using the convenience sampling technique among all those who received Covid-19 services during the past six months in the city of Tehran. Results: The mean age of participants was 45.9 ± 15.9 and 51.5% were female. On an average, 52.6% of the respondents evaluated at least one dimension of responsiveness as appropriate and/or strongly appropriate. Communication obtained the highest score (58.2%), followed by confidentiality (56.5%), dignity (56%), and prompt attention (52%). Meanwhile, autonomy and choice were evaluated as poor (moderate, weak, and strongly weak) by 63.5 and 52.5% of respondents. There was no significant association between the type of healthcare center (i.e., public or private) and responsiveness (p-value = 0.896). However, there was a significant difference between gender (p-value = 0.036) and education level (p-value = 0.014) with responsiveness. According to the respondents, prompt attention and choice were the most and least important dimensions, respectively. Conclusions: Evaluation of HSR in the era of COVID-19 not only provides a tool for qualitative assessment of services but also plays an important role in providing feedback to policymakers to adopt effective policies.

The Impact of Adding Prandial Insulin to a Basal Based Regimen with Insulin Glargine in Type 2 Diabetic Patients.

Background: Type 2 diabetes (T2D) is a progressive disease that should be managed with insulin in case of oral glucose lowering drugs (OGLDs) failure. If basal insulin is not sufficient, rapid acting insulin will be added before the largest meal. We assessed the impact of adding one prandial insulin to a basal based regimen and insulin glargine in patients with type 2 diabetes to measure the percentage of subjects achieving the HbA1c target by the end of 24 weeks of treatment in routine clinical practice. Methods: This study was a 24-week observational study of patients with T2D not adequately controlled with OGLDs and basal insulin, for whom the physician had decided to initiate prandial insulin. The study endpoint was assessed at visit 1 (baseline), visit 2 at week 12 (±1 week) and visit 3 at week 24 (±1 week). The percentage of patients who achieved HbA1c targets was assessed at week 24. Statistical analyses were performed using IBM SPSS for Windows v 19 (IBM, Armonk, New York, USA). Logistic regression analysis was used to detect predicting factors of achieving the HbA1c target by week 24. P<0.05 was considered as significant level. Results : Four hundred and eighteen patients with a mean±SD age of 56.24±9.85 years and a mean±SD duration of diabetes of 12.50±7.16 years were included. The median total daily dose of basal insulin was 24 units, while prandial insulin was started with 6 (4, 10) U/day, titrating up to 10 (8, 18) U/day at week 24. The daily dose of prandial insulin was the only factor that could significantly predict achieving targeted HbA1c by week 24 [OR: 1.04; 95% CI: 1.007,1.079; p-value: 0.019]. At week 24, 96 (22.9%) subjects achieved the HbA1c target with one prandial insulin. Conclusion : The results of our study suggest that "basal plus therapy" can lead to good glycemic control with a low risk of hypoglycemia and weight gain in patients with type 2 diabetes.

Loss of Time in the Treatment Adherence Process: A Qualitative Study in a Sample of Iranian People with Diabetes.

Diabetes is a significant public health problem and one of the causes of death and disability globally. One of the main problems with diabetes control is the lack of adherence to therapeutic regimens in people with diabetes. This study investigates the experiences and views of the Iranian people with diabetes to identify the challenges of the process of adherence to treatment. A grounded theory research design was used, incorporating in-depth interviews to collect the data. Using purposeful sampling, 28 people with type 2 diabetes (9 men, 19 women) from different places were included in the study. Constant comparative analysis was undertaken to identify key categories. The main challenge in this process is losing the golden time of preventing the complications of the disease that occurs for the following reasons: cultural habits and values, religious beliefs (believing diabetes was God's will), resistance to change due to age, job conditions, lack of harmony in the family, and non-shared decision-making in the health system. People with diabetes go through trial and error in order to achieve awareness and insight, and consequently, adherence to treatment. Therefore, they need help and support to achieve insight and adherence to treatment faster and without complications. In fact, if the care plan is designed to encourage active patient participation by the treatment team in the shortest possible time, the time to achieve compliance will be shorter and will have the least side effects for these people.

Practical Focus on American Diabetes Association/European Association for the Study of Diabetes Consensus Algorithm in Patients with Type 2 Diabetes Mellitus: Timely Insulin Initiation and Titration (Iran-AFECT).

BACKGROUND: The aim of this study was to evaluate the safety and effectiveness of insulin glargine in a large population from a variety of clinical care in Iranian people with type 2 diabetes mellitus (T2DM) and to measure the percentage of patients achieving glycosylated hemoglobin (HbA1c) <7% by the end of 24 weeks of treatment in routine clinical practice. METHODS: This study was a 24 week, observational study of patients with T2DM, for whom the physician had decided to initiate or to switch to insulin glargine. The safety and efficacy of glargine were assessed at baseline and at week 24. RESULTS: Seven hundred and twenty-five people with T2DM (63% female) including both insulin naïve and prior insulin users were recruited in this study. The mean age of the participants was 54.2±11.2 years, and the mean HbA1c level was 8.88%±0.93% at baseline. By the end of the study, 27% of the entire participants reached to HbA1c target of less than 7% and 52% had HbA1c ≤7.5%. No serious adverse event was reported in this study. Furthermore, overall hypoglycemia did not increase in prior insulin users and the entire cohort. In addition, body weight did not change in participants while lipid profile improved significantly. CONCLUSION: Treatment with insulin glargine could improve glycemic control without increasing the risk of hypoglycemic events in people with T2DM. In addition, a significant clinical improvement was observed in lipid profile.

Consequences of AphanizomenonFlos-aquae(AFA) extract (Stemtech (TM) ) on metabolic profile of patients with type 2 diabetes.

BACKGROUND: Blue- green algae is one of the most nutrient dense foods which is rich in substances that have useful effects on human health. The purpose of this study was to evaluate the effectiveness of a water- soluble extract of the cyanophyta Aphanizomenon Flos-aquae (Stemtech (TM) ) as a functional supplement on CD markers, lipid profile, glucose levels as well as its side effects in Iranian patients with type 2 diabetes. METHODS: During this randomized, double-blind, placebo-controlled trial 49 type 2 diabetic patients, aged between 20 and 60 years with a HbA1C ≥ 7.5 %, were allocated. Patients were divided into two groups of placebo and treated with an equal ratio 1:1. The subjects in StemtechTM group received one capsule of StemFlo (508 mg) before breakfast and two capsules of StemEnhance (500 mg) after each meal for a period of 12 weeks, and placebo group was instructed to take placebo with the same pattern. During the intervention period, subjects were asked to keep usual diet and prohibited to take any functional foods or dietary supplements. Metabolic panel has been measured as the primary outcome of study at the beginning and end of the intervention period via blood sampling. RESULTS: Stemtech (TM) supplementation for 12 weeks decreased fasting blood glucose (FBG) and Glycatedhemoglobin (HbA1c). Mean serum chemistry parameters (Triglyceride, Total Cholesterol, LDL, HDL, CRP, AST, ALT, BUN and Creatinine) as well as CD 34(+), IL-6, TNF-α in treated and control groups before and after the study showed no considerable dissimilarities. CONCLUSION: StemtechTM intervention brought in positive consequence on blood glucose levels in Iranian patients with type 2 diabetes, consequently suggests the Stemtech (TM) as a functional food for the management of diabetes.

Body composition in adults with newly diagnosed type 2 diabetes: effects of metformin.

BACKGROUND: The aim of this study was to measure the body composition in adults with newly diagnosed type 2 diabetes mellitus and to explore the effect of metformin therapy on the various components of body composition, insulin sensitivity, and glucose homeostasis. METHODS: This was an observational study consisted of 51 newly diagnosed people with type 2 diabetes on 1000 mg metformin twice daily for 6 months. The body composition of each subject was measured by dual energy X-ray absorptiometry at enrollment and 24 weeks after metformin mono-therapy. Sarcopenia was defined and compared based on the ratio of appendicular skeletal muscle and height squared, skeletal muscle index and residual methods. Homeostasis model assessment-insulin resistance and Quantitative Insulin Sensitivity Check Index were used for estimating insulin sensitivity. The level of physical activity was assessed using self-administered International physical Activity questionnaire. RESULTS: Forty one subjects (80.4%) completed the study. The mean age of the participants was 52.67 ± 10.43 years. Metformin treatment was associated with a significant decrease in total fat mass (-1.6 kg, P = 0.000). By week 24, the lean to fat ratio increased (P = 0.04) with men showing greater significant changes. Twenty percent of the female participants were detected to have sarcopenia. In addition, there was a significant improvement of glucose homeostasis and insulin sensitivity. CONCLUSIONS: Metformin therapy results in significant improvement in body composition and insulin sensitivity of adults with newly diagnosed type 2 diabetes. Furthermore, sarcopenia begins in women with diabetes much earlier than expected as an age related phenomenon.