Expert eValuation of Efficacy and Rationality of Vildagliptin "EVER-Vilda": An Indian Perspective.

Vildagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor is effective in reducing HbA1c levels in patients with type 2 diabetes (T2DM) when administered as monotherapy, dual or triple combination therapy. In India, Vildagliptin is commonly prescribed in T2DM patients because it reduces mean amplitude of glycemic excursion (MAGE), has lower risk of hypoglycemia and is weight neutral. Early combination therapy with vildagliptin and metformin is effective and well-tolerated in patients with T2DM, regardless of age or ethnicity. In view of already existing data on vildagliptin and the latest emerging clinical evidence, a group of endocrinologists, diabetologists and cardiologists convened for an expert group meeting to discuss the role and various combinations of vildagliptin in T2DM management. This practical document aims to guide Physicians and Specialists regarding the different available strengths and formulations of vildagliptin for the initiation and intensification of T2DM therapy.

Discharge Planning for People with Inpatient Hyperglycaemia: A Review on Pharmacological Management.

Inadequate glycaemic control post-discharge is the root cause of readmission in people with diabetes mellitus (DM) and is often linked to improper discharge planning (DP). A structured DP plays a crucial role in ensuring continuing home care and avoiding readmissions. DP should help patients in self-care and provide appropriate guidance to maintain optimal glycaemic control. There is a scarcity of reports and recommendations on the proper DP for people with DM on insulin therapy. The present review provides important consideration based on experts' opinions from the National Insulin and Incretin summit (NIIS), focusing on the effective treatment strategies at the time of discharge, especially for insulin therapy. A review of literature from PubMed and Embase was conducted. The consensus was derived, and recommendations were made on effective DP for patients with DM. Recommendations were drawn at the NIIS for post-discharge treatment for medical and surgical cases, stress-induced hyperglycaemia, elderly, pregnant women, and coronavirus disease 2019 (COVID-19) cases. The committee also recommended a comprehensive checklist to assist the physicians during discharge.

Cost-effectiveness of a multicomponent quality improvement care model for diabetes in South Asia: The CARRS randomized clinical trial.

OBJECTIVES: To assess the cost-effectiveness of a multicomponent strategy versus usual care in people with type 2 diabetes in South Asia. DESIGN: Economic evaluation from healthcare system and societal perspectives. SETTING: Ten diverse urban clinics in India and Pakistan. PARTICIPANTS: 1146 people with type 2 diabetes (575 in the intervention group and 571 in the usual care group) with mean age of 54.2 years, median diabetes duration: 7 years and mean HbA1c: 9.9% (85 mmol/mol) at baseline. INTERVENTION: Multicomponent strategy comprising decision-supported electronic health records and non-physician care coordinator. Control group received usual care. OUTCOME MEASURES: Incremental cost-effectiveness ratios (ICERs) per unit achievement in multiple risk factor control (HbA1c <7% (53 mmol/mol) and SBP <130/80 mmHg or LDLc <2.58 mmol/L (100 mg/dL)), ICERs per unit reduction in HbA1c, 5-mmHg unit reductions in systolic BP, 10-unit reductions in LDLc (mg/dl) (considered as clinically relevant) and ICER per quality-adjusted life years (QALYs) gained. ICERs were reported in 2020 purchasing power parity-adjusted international dollars (INT$). The probability of ICERs being cost-effective was considered depending on the willingness to pay (WTP) values as a share of GDP per capita for India (Int$ 7041.4) and Pakistan (Int$ 4847.6). RESULTS: Compared to usual care, the annual incremental costs per person for intervention group were Int$ 1061.9 from a health system perspective and Int$ 1093.6 from a societal perspective. The ICER was Int$ 10,874.6 per increase in multiple risk factor control, $2588.1 per one percentage point reduction in the HbA1c, and $1744.6 per 5 unit reduction in SBP (mmHg), and $1271 per 10 unit reduction in LDLc (mg/dl). The ICER per QALY gained was $33,399.6 from a societal perspective. CONCLUSIONS: In a trial setting in South Asia, a multicomponent strategy for diabetes care resulted in better multiple risk factor control at higher costs and may be cost-effective depending on the willingness to pay threshold with substantial uncertainty around cost-effectiveness for QALYs gained in the short term (2.5 years). Future research needs to confirm the long-term cost-effectiveness of intensive multifactorial intervention for diabetes care in diverse healthcare settings in LMICs.

Real-world safety and effectiveness of iGlarLixi in people with type 2 diabetes who fast during Ramadan: The SoliRam observational study.

BACKGROUND AND AIMS: To evaluate the safety and effectiveness of iGlarLixi in adults with type 2 diabetes (T2D) fasting during Ramadan. METHODS: SoliRam was a multinational, prospective, single-arm, real-world observational study conducted during Ramadan 2020 and 2021 in adults with T2D treated with iGlarLixi ≥3 months at study entry. The primary endpoint was the percentage of participants experiencing ≥1 episode of severe and/or symptomatic documented hypoglycemia (<70 mg/dL [<3.9 mmol/L]). RESULTS: Among the 409 eligible participants followed during Ramadan, 96.8% fasted for ≥25 days and 92.4% did not break fasting during Ramadan. Four participants broke their fast due to hypoglycemia. Minimal adjustments were seen in antihyperglycemic therapies from pre to during Ramadan. Documented symptomatic hypoglycemia was experienced by 1.0%, 2.3%, and 0.3% of participants, respectively, during the last month of pre-Ramadan, Ramadan, and first month post-Ramadan. Mean change in HbA1c from pre-to post-Ramadan periods was -0.75% (-8.2 mmol/mol), and participants with HbA1c <7% (<53 mmol/mol) increased from 7.9% pre-Ramadan to 28.6% post-Ramadan. CONCLUSIONS: iGlarLixi is an effective and well-tolerated therapy for people with T2D, including those who intend to fast during Ramadan, and is associated with a low risk of hypoglycemia; benefits were observed both during and after Ramadan.

Use of Second-Generation Basal Insulin Gla-300 in Special Populations: A Narrative Mini-Review.

BACKGROUND AND AIMS: Hypoglycemia and insulin-related adverse events are crucial barriers to effective diabetes management, particularly in the elderly, people with renal impairment, people with diabetes fasting during Ramadan, or people with type 1 diabetes mellitus (T1DM). There is a scarcity of clinical and real-world evidence assessing the effectiveness and safety of insulin glargine 300 U/mL (Gla-300) in these special populations. To understand the entirety of evidence, this mini-review elaborates on the use of Gla-300 in diabetes management among special populations. METHODS: Clinical and real-world evidence related to the use of Gla-300 among special populations with diabetes were retrieved using PUBMED and Google Scholar. RESULTS: Gla-300 has shown improved glycemic control with stable insulin action and low risk of hypoglycemia in diverse groups with diabetes. It also appears to have an acceptable safety profile during Ramadan fasting. However, adequate monitoring and adjustment of insulin dose on an individual basis should be considered. CONCLUSION: Gla-300 is a second-generation basal insulin with proven benefits of reduced risk of hypoglycemia and improved glycemic control in special populations of people with diabetes.

Incorporating Integrated Personalised Diabetes Management (iPDM) in Treatment Strategy: A Pragmatic Approach.

Diabetes is a global public health concern. Vigilant monitoring and effective management of glycaemic variations are essential to prevent complications of diabetes. Effectively incorporating monitoring strategies in management of diabetes is a serious challenge. Patient-centered approach is necessary to customise monitoring and therapy of diabetes. This has been made possible by integrating technology with personalised therapeutic strategy. The integrated personalised diabetes management (iPDM) is a holistic, patient-centered approach that focuses on personalising diabetes management to streamline therapy and improve outcome. iPDM helps strengthen the care process, facilitates communication between patients and their healthcare team, and integrates digital tools that visualise and analyse data. The five E's which includes enthusiasm, education, expertise, empathy and engagement are the key pillars of a strong foundation for the iPDM model. iPDM model is a convenient and easily accessible tool that shifts the management paradigm from an "algorithmic" to "personalized" care to optimise treatment outcomes. Structured self-monitoring of blood glucose (SMBG) should be available as part of the self-management process for people with sub-optimally controlled type 2 diabetes, including those not on insulin therapies. Different SMBG regimens should be followed based on factors such as diabetes type, treatment approach (diet, oral antidiabetic medication, or insulin), glycaemic control, available resources, and patient's level of education.

Glimepiride and Metformin Combinations in Diabetes Comorbidities and Complications: Real-World Evidence.

Objective To evaluate the usage of various strengths of glimepiride and metformin fixed-dose combinations in the management of type 2 diabetes mellitus (T2DM) patients with comorbidities and complications. Methods A retrospective, non-randomized, non-comparative, multi-centric real-world study included T2DM patients (age > 18 years) taking glimepiride and metformin fixed-dose combinations. Age, duration of diabetes, diabetes complications, comorbidities (hypertension and dyslipidemia), dosage frequency, and concomitant medications were analyzed from medical charts. Results A total of 4858 T2DM patients were included, with a mean age of 52.67 years and males being predominant in the study population (60.85%). The laboratory investigations showed a mean glycated hemoglobin (HbA1c) of 7.5, low-density lipoprotein (LDL) cholesterol of 104.81 ± 38.19 mg/dL, and serum creatinine of 0.88 ± 0.26 mg/dL. Around 2055 (42.30%) T2DM patients were hypertensive, and telmisartan alone and a telmisartan-based combination were the drugs of choice for hypertension management. Similarly, 1073 (22.08%) T2DM patients were having dyslipidemia and were primarily managed with rosuvastatin and its combination in 664 (62%) patients. Macrovascular complications were observed in 339 (6.97%) T2DM patients, among which coronary artery disease (CAD) had maximum prevalence, affecting 273 (5.61%) T2DM patients. Microvascular complications were 1010 (20.79%) T2DM patients, among which neuropathy had affected a maximum of 686 (14.12%) followed by retinopathy (2.34%) and nephropathy (1.81%). Among the available 11 strengths, the glimepiride 2 mg and metformin 500 mg combination were most widely prescribed in 1297 (26.69%), followed by glimepiride 1 mg and metformin 500 mg in 1193 (24.57%) patients, and the preferred dosage pattern was twice a daily in 2665 (54.85%) T2DM patients. An age-wise prescription analysis showed that glimepiride and metformin combinations were the preferred choice for the management of diabetes across all the age groups. Conclusion The real-world evidence in the Indian clinical setting indicates that glimepiride and metformin fixed-dose combinations are widely used in the management in T2DM patients with comorbidities like hypertension, dyslipidemia, and diabetes complications. Glimepiride and metformin fixed-dose combinations are suitable for early as well as long-standing diabetes.

Consensus Recommendations on GLP-1 RA Use in the Management of Type 2 Diabetes Mellitus: South Asian Task Force.

The advent of incretin mimetics such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) has enriched the armamentarium for diabetes management owing to their glycaemic as well as extra-glycaemic benefits. The approval status and availability of this class of drugs vary widely across the globe. Being a relatively newer class of drug with numerous benefits, several national and international guidelines are working towards addressing clinical questions pertaining to the optimal use of GLP-1 RAs for the management of diabetes. Although the newer class of drugs are associated with significant benefits such as patient-centric approach, these drugs demand the providers to be vigilant and knowledgeable about the medication. The South Asian population is at higher risk of type 2 diabetes mellitus (T2DM) because of their genetic predisposition and lifestyle changes. Hence, prevention and management of T2DM and its associated complications in this population are of paramount importance. The current report aims to present an overview of current knowledge on GLP-1 RAs based on pragmatic review of the available clinical evidence. In addition, this report is a consensus of expert endocrinologists representing South Asian countries including India, Pakistan, Bangladesh, Nepal, Sri Lanka, Afghanistan and the Maldives on essential recommendations related to the use of GLP-1 RAs in a real-world scenario.

Lilly Insulin Glargine Versus Lantus® in Type 2 Diabetes Mellitus Patients: India and East Asia Subpopulation Analyses of the ELEMENT 5 Study.

BACKGROUND AND OBJECTIVES: Lilly insulin glargine (LY IGlar; Basaglar®) and the reference insulin glargine product (IGlar; Lantus®) are basal insulin glargine analogs with identical amino acid sequence and similar pharmacological profiles. ELEMENT 5, a Phase 3, prospective, randomized, multinational, two-arm, active-controlled, open-label, parallel-design study in type 2 diabetes mellitus (T2DM) patients (N = 493) showed similar efficacy and safety profiles with LY IGlar and IGlar. This study reports results from India (N = 100) and East Asia (N = 134) subpopulations. METHODS: Patients from India and East Asia (Korea and Taiwan) with T2DM who were insulin naïve (glycated hemoglobin (HbA1c) ≥ 7.0% and ≤ 11.0%) or on basal insulin (HbA1c ≤ 11.0%) were randomized to receive LY IGlar or IGlar along with oral antihyperglycemic medications (OAMs) for 24 weeks. Patients were instructed to self-titrate from the starting dose by 1 unit/day until fasting blood glucose (FBG) ≤ 5.6 mmol/L (100 mg/dL) was achieved. The key outcome was HbA1c change from baseline to Week 24. RESULTS: Within-group least-squares mean (LSM) decrease (baseline to Week 24) in HbA1c was similar between treatments. The upper limit of confidence interval (CI) for treatment difference was below the defined 0.4% noninferiority margin in India (LY IGlar: - 0.83%; IGlar: - 0.62%; difference [95% CI] - 0.21 [- 0.70, 0.28]) and East Asia (LY IGlar: - 1.28%; IGlar: - 1.26%; difference [95% CI] - 0.02 [- 0.34, 0.30]) subpopulations. Results of other efficacy and safety endpoints at Week 24 were similar between treatments in both subpopulations. LSM self-monitored FBG levels were similar between treatments at all visits in both subpopulations except at Week 24 in the India subpopulation (LY IGlar: 5.65 [0.10] mmol/L or 101.8 [1.86] mg/dL; IGlar: 5.18 [0.10] mmol/L or 93.3 [1.75] mg/dL; p = 0.002). CONCLUSION: Efficacy and safety profiles of LY IGlar and IGlar, in combination with OAMs, were similar in India and East Asia subpopulations. This was consistent with the ELEMENT 5 total population. CLINICAL TRIAL REGISTRATION: NCT02302716.

Rationale and protocol for estimating the economic value of a multicomponent quality improvement strategy for diabetes care in South Asia.

BACKGROUND: Economic dimensions of implementing quality improvement for diabetes care are understudied worldwide. We describe the economic evaluation protocol within a randomised controlled trial that tested a multi-component quality improvement (QI) strategy for individuals with poorly-controlled type 2 diabetes in South Asia. METHODS/DESIGN: This economic evaluation of the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) randomised trial involved 1146 people with poorly-controlled type 2 diabetes receiving care at 10 diverse diabetes clinics across India and Pakistan. The economic evaluation comprises both a within-trial cost-effectiveness analysis (mean 2.5 years follow up) and a microsimulation model-based cost-utility analysis (life-time horizon). Effectiveness measures include multiple risk factor control (achieving HbA1c < 7% and blood pressure < 130/80 mmHg and/or LDL-cholesterol< 100 mg/dl), and patient reported outcomes including quality adjusted life years (QALYs) measured by EQ-5D-3 L, hospitalizations, and diabetes related complications at the trial end. Cost measures include direct medical and non-medical costs relevant to outpatient care (consultation fee, medicines, laboratory tests, supplies, food, and escort/accompanying person costs, transport) and inpatient care (hospitalization, transport, and accompanying person costs) of the intervention compared to usual diabetes care. Patient, healthcare system, and societal perspectives will be applied for costing. Both cost and health effects will be discounted at 3% per year for within trial cost-effectiveness analysis over 2.5 years and decision modelling analysis over a lifetime horizon. Outcomes will be reported as the incremental cost-effectiveness ratios (ICER) to achieve multiple risk factor control, avoid diabetes-related complications, or QALYs gained against varying levels of willingness to pay threshold values. Sensitivity analyses will be performed to assess uncertainties around ICER estimates by varying costs (95% CIs) across public vs. private settings and using conservative estimates of effect size (95% CIs) for multiple risk factor control. Costs will be reported in US$ 2018. DISCUSSION: We hypothesize that the additional upfront costs of delivering the intervention will be counterbalanced by improvements in clinical outcomes and patient-reported outcomes, thereby rendering this multi-component QI intervention cost-effective in resource constrained South Asian settings. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01212328.

Consensus on Initiation and Intensification of Premix Insulin in Type 2 Diabetes Management.

INTRODUCTION: Premix insulin is the most commonly used insulin preparation in India. The first Indian premix guidelines were developed in 2009 and thereafter were updated in 2013. There is a need to revisit the Indian premix insulin guidelines, in view of emerging evidence and introduction of newer co-formulations. OBJECTIVE: The present consensus has been developed to evaluate available premix formulations, examine existing evidence related to premix formulations, and evolve consensus statement of recommendations on the topic. METHODS: A meeting of experts from across India was conducted at Chennai in July 2016. The expert committee evaluated each premix insulin regimen with reference to 1) Current recommendations by various guidelines, 2) Approved pack inserts and 3) Published scientific literature. The information was debated and discussed within the expert group committee, to arrive at seven consensus-based recommendations for initiation and intensification with premix insulin. RESULTS: Recommendations based on consensus on initiation and intensification of premix insulin in type 2 diabetes mellitus (T2DM) management were developed for the following situations. 1) Initiation of premix insulin co-formulation at diagnosis, 2) Initiation of once daily (OD) premix insulin/co-formulation, 3) Initiation of twice daily (BID) premix insulin/co-formulation 4) Intensification with BID and thrice daily (TID) premix insulin/co-formulation. Three recommendations pertained to the use of premix insulin in other forms of diabetes, or in specific situations: 5) Use of premix insulin in gestational diabetes mellitus 6) Use of premix insulin in type 1 Diabetes Mellitus (T1DM) 7) Premix insulin use during Ramadan. CONCLUSIONS: In the setting of high carbohydrate consumption in India, or in patients with predominant post prandial hyperglycemia, premix insulin/co-formulation can offer effective and convenient glycemic control. This paper will help healthcare practitioners initiate and intensify premix insulin effectively.