Fixed-Dose Combination of Canagliflozin and Metformin as an Adjunct to Diet and Exercise in Indian Adults with Type 2 Diabetes Mellitus: Results from a Multicentric, Open-Label, Single-Arm, Phase IV Study.

BACKGROUND: Canagliflozin and metformin fixed-dose combination (CANA/MET FDC), an approved treatment for type 2 diabetes mellitus (T2DM) in India, effectively lowers glycated hemoglobin (HbA1c), promotes weight loss, and improves patient adherence. As a regulatory requirement, we aimed to evaluate the safety and efficacy of CANA/MET FDC in Indian patients with T2DM. RESEARCH DESIGN AND METHODS: This prospective, multicenter, open-label, single-arm, phase IV study included Indian patients with T2DM (aged 18-65 years) inadequately controlled on diet and exercise. Patients received CANA/MET (50/500 and 50/1000 mg) immediate-release (IR) FDC twice daily for 24 weeks. The primary endpoint was safety assessment, including adverse events (AEs) and serious AEs (SAEs). The secondary endpoint included a change in HbA1c from baseline to weeks 12 and 24. Descriptive statistics were used for all continuous safety variables and efficacy parameters. RESULTS: Of the 310 patients screened, 276 were enrolled. 114/274 (41.6%) patients had ≥1 treatment-emergent AE [treatment-emergent AEs (TEAEs), among which 29 (10.6%) were related to study intervention]. The most common TEAEs were dyslipidemia (4.7%), pyrexia (4.7%), genital infections (3.3%), hypoglycemia (3.3%), and urinary tract infections (2.6%). Three (1.1%) patients had serious TEAEs, and all cases were resolved. No deaths were reported. The mean change in HbA1c from baseline was -0.92 and -0.93% at weeks 12 and 24, respectively. CONCLUSION: The study demonstrates the safety and efficacy of CANA/MET FDC in Indian patients with T2DM, presenting a safe therapeutic option for diabetes management in India.

Prevalence of Pancreatic Exocrine Insufficiency among Patients with Diabetes Mellitus in India.

AIMS: We aimed to assess the prevalence of pancreatic exocrine insufficiency (PEI) in Indian patients with type 1 diabetes (T1D) or type 2 diabetes (T2D) using a unique diagnostic criterion. METHODS: This multicenter study included patients aged ≥18 years with diabetes for at least 5 years. The sociodemographic characteristics, lifestyle habits, and clinical characteristics of patients were assessed. Patients were administered the PEI questionnaire (PEI-Q), and fecal elastase-1 (FE) concentration was measured. Patients were diagnosed to have PEI if they satisfied any two of the following three criteria: (a) a PEI-Q total symptom score of ≥0.60; (b) presence of malnutrition using the European Society of Clinical Nutrition and Metabolism diagnostic criteria for malnutrition; or (c) FE concentration <100 µg/gm stool. RESULTS: This multicenter study included patients aged ≥18 years with diabetes for at least 5 years. The sociodemographic characteristics, lifestyle habits, and clinical characteristics of patients were assessed. Patients were administered the PEI questionnaire (PEI-Q), and fecal elastase-1 (FE) concentration was measured. Patients were diagnosed to have PEI if they satisfied any two of the following three criteria: (a) a PEI-Q total symptom score of ≥0.60; (b) presence of malnutrition using the European Society of Clinical Nutrition and Metabolism diagnostic criteria for malnutrition; or (c) FE concentration <100 µg/gm stool. CONCLUSIONS: Pancreatic exocrine insufficiency (PEI) was found to be prevalent in nearly one-fourth of Indian patients with diabetes, using composite diagnostic criteria.

Expert Opinion by Clinicians on the Use of Insulin Therapy in People with Hepatic Impairment.

People with type 2 diabetes mellitus (T2DM) have a higher risk of developing chronic liver disease (CLD) and its complications. T2DM, obesity, and insulin resistance are all strongly associated with nonalcoholic fatty liver disease (NAFLD). Conversely, people suffering from cirrhosis have reduced glucose tolerance in approximately 60% of cases, diabetes in 20% of cases, and insulin-mediated glucose clearance is lowered by 50% as compared with those who do not have cirrhosis. An exploratory review was conducted using existing published evidence from clinical studies on dosing and titrations of individual insulin formulations in people with CLD to optimize insulin dosage titration for minimizing hypoglycemia risk.pThis article discusses current hyperglycemia treatment techniques for patients with CLD as well as the consensus recommendations on insulin use in special populations with T2DM and hepatic impairment. Based on available evidence and expert diabetologists' recommendations, careful insulin dose titration, customized glycemic targets, and frequent glucose screening are recommended for optimal glycemic management without hypoglycemia in CLD. Long-acting insulin should be avoided or used when short-acting insulin fails to provide adequate glycemic control with raised fasting blood sugar levels. While the patient's glucose profile is being evaluated, the prandial insulin dose can be lowered by 25% initially. The dose can be titrated based on the patient's postprandial glycemic expression and whether their food intake meets the Child-Pugh scores A and B categories. Titrating premixed insulins is difficult for patients in class C since their appetite and overall health are constantly compromised and in flux.

Adherence and Swallowing Experience with a Modified, Smaller-sized Tablet Formulation of Metformin and Glimepiride (SR) in Indian Patients with Type 2 Diabetes Mellitus.

BACKGROUND: This study evaluated the adherence and swallowing experience with novel oval-shaped, compact-sized metformin (500 mg/1000 mg)-glimepiride (1mg/2mg) combination, sustained-release tablet (Gluformin G1/Gluformin G2 SR; GM-new-SR) in Indian patients with T2DM, previously treated with conventional metformin-glimepiride combination tablet. METHODS: Patients' adherence, swallowing experience, and satisfaction were assessed at baseline and month-3 by Adherence to Refills and Medication Scale (ARMS12; adherent: ARMS12 score=12; nonadherent: ARMS12 score >12) and questionnaire based 5-point Likert scale, respectively. Safety was also assessed. RESULTS: Of 1550 patients enrolled, 1547 (99.8%) completed the study. After 3 months of switching to GM-new-SR tablets, adherence rate increased from 4.38% to 91.1%, with concurrent reduction in mean ARMS-12 score by 6.3±4.36 (p<0.0001). Compared to baseline, all glycemic indices, HbA1c, PPG, and FPG, significantly improved (p<0.0001) in the overall population. Reduction in HbA1c levels was significant only in patients who were adherent to therapy as opposed to nonadherent patients (7.8±1.74 to 7.1±0.85, p<0.0001 vs. 7.7±1.39 to 6.7±0.77, p=0.4276). Most patients attributed ease of swallowing of GM-new-SR tablets to its modified shape (95.5%) and size (94.9%). Most patients (90.4%) were satisfied with the new tablet formulation. Size of the tablet was the most common reason for patients' nonadherence with conventional tablets, which was reported to be less frequent with GM-new-SR tablets (2.5% vs 53.4%). CONCLUSION: Treatment with GM-new-SR tablets significantly increased adherence and was associated with improvement in glycemic indices, which could be attributed to the compact shape and size of the new tablet formulation.

A Real-World Observational Study of Gla-300 in Adults with Type 2 Diabetes Who Fast During Ramadan in the South Asia Region: A Subgroup Analysis of the ORION Study.

INTRODUCTION: In this ORION study subgroup analysis, the safety and effectiveness of insulin glargine 300 U/mL (Gla-300) was evaluated in people from the South Asia region with type 2 diabetes mellitus (T2DM) before, during, and after Ramadan, in a real-world setting. METHODS: The ORION study was a real-world, prospective, observational, non-comparative study conducted across 11 countries. The current subgroup analysis included participants from the South Asia region (India and Pakistan) who fasted during Ramadan. The primary endpoint was the percentage of participants experiencing ≥ 1 event of severe and/or symptomatic documented hypoglycemia with self-monitored plasma glucose (SMPG) ≤ 70 mg/dL during Ramadan. Secondary endpoints analyzed were changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), SMPG, insulin dose, and adverse events (AEs). RESULTS: This subgroup analysis included 106 participants from the South Asia region with mean (standard deviation) age of 51.3 (10.9) years and mean number of 29.8 (4.0) fasting days. The number of severe and/or symptomatic documented hypoglycemia events was low in the pre-Ramadan (SMPG ≤ 70 mg/dL: 1 event [0.9%]; SMPG < 54 mg/dL: 1 event [0.9%]) and Ramadan periods (SMPG ≤ 70 mg/dL: 1 event [0.9%]; SMPG < 54 mg/dL: 0 events), and none in the post-Ramadan period. One participant reported severe hypoglycemia (any time of the day: nocturnal or daytime) throughout the pre-Ramadan period. A reduction in HbA1c and FPG levels was seen during the pre- to post-Ramadan period; however, a slight increase in SMPG levels was reported during this same period. Gla-300 daily dose was reduced from 21.6 (9.6) U to 20.2 (8.9) U during the pre-Ramadan to Ramadan period. The incidence of AEs was 1.9%. CONCLUSIONS: The real-world data from the ORION study indicate that Gla-300 is effective, with low risk of hypoglycemia, for the management of T2DM during Ramadan in the South Asian population. TRIAL REGISTRATION: CTRI/2019/02/017636.

A Prospective Multicentric Postmarketing Observational Study to Characterize the Patient Population with Reduced Gastrointestinal Motility among Indian Diabetic Patients Receiving Itopride: The Progress Study.

AIMS: This study was intended to assess the clinical profile of Indian diabetic patients with reduced gastrointestinal (GI) motility and to understand the role of itopride in addressing reduced GI motility (gastroparesis) symptoms and maintaining glycemic control. MATERIAL AND METHODS: Patients with established reduced GI motility (scintigraphy), with varying degree of GI symptoms, receiving itopride 150 mg as per physicians' discretion were enrolled. Clinical profile, changes in symptom severity, glycemic indices, tolerability, and quality of life (QoL) after 8-week therapy (Patient assessment of upper GI disorders-QoL [PAGI-QoL]) were assessed. RESULTS: Mean ± standard deviation age of enrolled population (n = 41) was 51.8 ± 12.39 years. Average duration of gastroparesis since underlying etiology was 67.7 ± 59.76 months. Common symptoms reported at baseline were bloating (68.3%), postprandial fullness (61.0%), nausea (51.2%), early satiety (41.5%), heartburn (39.0%), and vomiting (9.8%). Itopride therapy resulted in significant improvement in all symptoms (P < 0.001), which correlated with improved QoL (PAGI-QoL score reduction: 13.8 ± 11.48; P < 0.0001). Moreover, significant improvement in glycemic indicators was also evident (mean change from baseline hemoglobinA1c -0.5 ± 1.18; fasting plasma glucose -15.3 ± 43.61; postprandial plasma glucose -24.6 ± 57.20). CONCLUSIONS: Itopride showed effectiveness in addressing symptoms of reduced GI motility in diabetics, with improved QoL. Significant improvement in glycemic indices was also evident posttreatment with itopride. This study sheds light on the role of prokinetics, not only for symptom relief but also for improving glycemic control in diabetic patients with reduced GI motility, thus providing a holistic approach for the management of these patients.

Thyroid Dysfunction in Patients with Metabolic Syndrome: A Cross-Sectional, Epidemiological, Pan-India Study.

BACKGROUND: This study was conducted to assess the prevalence and clinical and epidemiological factors of thyroid dysfunction (TD) in Indian patients diagnosed with metabolic syndrome (MetS). METHODS: In this cross-sectional study, 432 adults with an established diagnosis of MetS were enrolled across ten centers in India. Anthropometric measurements and vital signs were noted. Blood samples were tested for hemogram, coagulogram, lipid profile, and thyroid function. Fasting plasma glucose (FPG) and fasting plasma insulin were used for the calculation of homeostasis model assessment-estimated insulin resistance (HOMA-IR). Overt hypothyroidism was defined as thyroid-stimulating hormone (TSH) > 4.50 µIU/mL with free thyroxine (FT4) < 0.8 ng/dL and free triiodothyronine (FT3) < 1.4 pg/mL; subclinical hypothyroidism as TSH > 4.50 µIU/mL with FT4 = 0.8-1.8 ng/dL and FT3 = 1.4-4.4 pg/mL; overt hyperthyroidism as TSH < 0.45 µIU/mL with FT4 > 1.8 ng/dL and FT3 > 4.4 pg/mL; and subclinical hyperthyroidism as TSH < 0.45 µIU/mL with FT4 = 0.8-1.8 ng/dL and FT3 = 1.4-4.4 pg/mL. RESULTS: About 121 out of 432 patients (28%) were diagnosed with TD (mean age ± SD: 47.9 ± 10.96 years), with women predominance (75% versus 25%). Most patients were in the >45 years of age group (men: 63%; women: 59%). TD was associated with high waist circumference (99.17%), reduced high-density lipoprotein-C (87.60%), raised HOMA-IR (86.78%), systolic blood pressure (77.69%), diastolic blood pressure (59.50%), fasting glucose (58.68%), and triglycerides (33.06%). Overt hypothyroidism was reported in 17.59% (N = 76) of patients. Subclinical hypothyroidism, overt hypothyroidism, and subclinical hyperthyroidism were reported in 8.10%, 1.60%, and 0.70% patients with newly occurred TD, respectively. No case of overt hyperthyroidism was present in these patients. CONCLUSION: Hypothyroidism was the most common TD in Indian patients with MetS. A large proportion of TD cases diagnosed during the study highlight the need for vigilant thyroid screening in patients with MetS in a real-life setting.