Effectiveness of Dapagliflozin as Add-On to Metformin with or without Other Oral Antidiabetic Drugs in Type 2 Diabetes Mellitus: A Multicentre, Retrospective, Real-World Database Study.

BACKGROUND: Real-world Indian studies evaluating effectiveness of dapagliflozin as an add-on to other oral antidiabetic drugs (OAD) in patients with type 2 diabetes mellitus (DM) are scarce. METHODS: An electronic medical record (EMR)-based, retrospective, multicentre study was conducted to evaluate the effectiveness of dapagliflozin as add-on therapy in adult patients with inadequately controlled DM on metformin with or without other OAD. Baseline characteristics (visit 1: metformin or metformin plus OAD treatment for at least 30 days) and treatment-related outcomes (visit 2: follow-up) considered between 60 and 140 days after adding/switching dapagliflozin [glycated haemoglobin (HbA1c), body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressure (DBP)] were analysed. RESULTS: A total of 3616 patients were screened from 478 centres. Most patients had received dapagliflozin (D) + metformin (M) + at least one other OAD [D + M + OAD, n = 2907 (80.4%), 408 followed-up with HbA1c reported], while 709 patients (19.6%, 138 followed-up with HbA1c reported) received dapagliflozin + metformin (D + M). Treatment with dapagliflozin as an add-on therapy resulted in significant change in HbA1c (-1.1 ± 1.44%; p < 0.05 for HbA1c subgroup ≥ 7.5%; -1.6 ± 1.41%; p < 0.05 for HbA1c subgroup ≥ 8%) at visit 2 compared with visit 1. Significant change in body weight (-1.4 ± 3.31 kg; p < 0.05 for HbA1c subgroup ≥ 7.5%; - 1.5 ± 3.22 kg; p < 0.05 for HbA1c subgroup ≥ 8%) was observed at visit 2. Similarly, a significant change in BMI was noted for the HbA1c subgroup ≥ 7.5% (-1.0 ± 8.38 kg/m2). However, the change in BMI in the HbA1c subgroup ≥ 8% was noted to be -1.4 ± 10.4 kg/m2, which was not statistically significant (p = 0.08). In the overall study population, significant change in the SBP (-4.5 ± 14.9 mmHg; p < 0.05 for HbA1c subgroup ≥ 7.5%; -4.5 ± 15.1 mmHg; p < 0.0001 for HbA1c subgroup ≥ 8%) was observed at visit 2 compared with visit 1. On identical lines, significant change in DBP (-1.5 ± 8.94 mmHg; p < 0.05 for HbA1c subgroup ≥ 7.5%; -1.4 ± 8.91 mmHg; p < 0.05 for HbA1c subgroup ≥ 8%) was noted. CONCLUSIONS: Dapagliflozin showed significant improvement in glycemic parameter, BMI and BP when added to metformin, with or without other OADs in a real-world scenario.

Nutritional Status of Underprivileged Indian Children and Youth with Type-1 Diabetes - A Multicentre Study.

Background: India has the highest number of prevalent type-1 diabetes (T1D) cases in the under-20-year age population. Data on the anthropometry of underprivileged Indian children with T1D are scarce. In economically disadvantaged countries like India, poor growth in patients with T1D is a major concern due to limited accessibility and affordability. Besides, due to the double burden of malnutrition, the prevalence of obesity is increasing mirroring the global trends, which may lead to the development of insulin resistance. Objectives: This study aims to assess the prevalence of malnutrition in Indian children and youth with T1D and to identify the determinants of short stature. Methods: A registry-based cross-sectional analysis of data collected from various centres across India enrolled in the Changing Diabetes in Children (CDiC) programme. Results: We observed that 6.4% were undernourished (3.4% severe undernutrition) and 17.7% (overweight 13.2%) had combined overweight/obesity. 21.2% of participants had short stature (adjusted for mid-parental height) with 7.4% cases of familial short stature. Longer duration of illness and insulin requirement were significant positive predictors of short stature while glycaemic control, insulin regimen and mid-parental height did not have a significant relationship with short stature. Participants on basal-bolus regimen had significantly higher insulin requirements and better glycaemic control than the ones on mixed-split regimen. Conclusion: We report that around one-fifth of children and youth with T1D were overweight/obese and around a fourth were stunted, especially those with longer duration of diabetes and higher insulin requirements. Close monitoring of anthropometric parameters is necessary for all children with T1D to optimize growth and nutrition.

The LongitudinAl Nationwide stuDy on Management And Real-world outComes of diabetes in India over 3 years (LANDMARC trial).

INTRODUCTION: LANDMARC (CTRI/2017/05/008452), a prospective, observational real-world study, evaluated the occurrence of diabetes complications, glycemic control and treatment patterns in people with type 2 diabetes mellitus (T2DM) from pan-India regions over a period of 3 years. METHODS: Participants with T2DM (≥25 to ≤60 years old at diagnosis, diabetes duration ≥2 years at the time of enrollment, with/without glycemic control and on ≥2 antidiabetic therapies) were included. The proportion of participants with macrovascular and microvascular complications, glycemic control and time to treatment adaptation over 36 months were assessed. RESULTS: Of the 6234 participants enrolled, 5273 completed 3 years follow-up. At the end of 3-years, 205 (3.3%) and 1121 (18.0%) participants reported macrovascular and microvascular complications, respectively. Nonfatal myocardial infarction (40.0%) and neuropathy (82.0%) were the most common complications. At baseline and 3-years, 25.1% (1119/4466) and 36.6% (1356/3700) of participants had HbA1c <7%, respectively. At 3-years, population with macrovascular and microvascular complications had higher proportion of participants with uncontrolled glycemia (78.2% [79/101] and 70.3% [463/659], respectively) than those without complications (61.6% [1839/2985]). Over 3-years, majority (67.7%-73.9%) of the participants were taking only OADs (biguanides [92.2%], sulfonylureas [77.2%] and DPP-IV inhibitors [62.4%]). Addition of insulin was preferred in participants who were only on OADs at baseline, and insulin use gradually increased from 25.5% to 36.7% at the end of 3 years. CONCLUSION: These 3-year trends highlight the burden of uncontrolled glycemia and cumulative diabetes-related complications, emphasizing the importance of optimizing diabetes management in India.

Study of Non-Thyroidal Illness Syndrome and Its Recovery in Critically Ill Patients at a Tertiary Care Centre in South India.

Background and Objectives: Transient thyroid hormone alterations are common during critical illness and are termed non-thyroidal illness syndrome (NTIS). We studied the prevalence of NTIS in the ICU setting and its impact on predicting mortality and other outcomes and compared it to the Acute Physiology and Chronic Health Evaluation II (APACHE II) score. Materials and Methods: The study included 119 consecutive patients admitted with a critical illness. APACHE II score was calculated. Total T3, total T4, TSH, free T3, and free T4 were measured at admission and after six weeks of discharge. NTIS and euthyroid groups were studied for ICU, hospital stays, mortality, readmission, and recovery. Predictors of mortality were compared between survivors and non-survivors. Results: The mean age was 60.15 ± 14.50 years with M:F = 84 (71%):35 (29%). NTIS was observed in 84 (71%), low T3 being the most common abnormality in 53 (63%). The occurrence of NTIS was significantly higher among non-survivors (28/30, 93%) versus survivors (56/89, 63%) (P = 0.002). Non-survivors showed significantly lower T3, TSH, and FT3/FT4 ratios and higher readmissions. NTIS group showed significantly greater ICU stay (P = 0.02) and had higher readmission rates (P = 0.032). Baseline T3 had the greatest power to predict mortality. APACHE II score also correlated significantly with mortality (19.60 ± 10.58 vs 11.99 ± 6.80, P < 0.001). The area under the curve (0.677) for the T3 level was lower than the APACHE II score (0.760). After six weeks, 61% had recovered from NTIS. Conclusions: NTIS was common amongst critically ill patients (71.5%), which reversed in 61% at six weeks. Low T3 was the most common abnormality and independently predicted mortality. Free T3/free T4 also significantly predicted mortality. The correlation between thyroid dysfunction and the severity of primary illness makes it an additional attractive low-cost marker of mortality.

Two-year trends from the LANDMARC study: A 3-year, pan-India, prospective, longitudinal study on the management and real-world outcome in patients with type 2 diabetes mellitus.

INTRODUCTION: There are limited data on the real-world management of diabetes in the Indian population. In this 2-year analysis of the LANDMARC study, the management of type 2 diabetes mellitus (T2DM) and related complications were assessed. METHOD: This multicenter, observational, prospective study included adults aged ≥25 to ≤60 years diagnosed with T2DM (duration ≥2 years at enrollment) and controlled/uncontrolled on ≥2 anti-diabetic agents. This interim analysis at 2 years reports the status of glycaemic control, diabetic complications, cardiovascular (CV) risks and therapy, pan-India including metropolitan and non-metropolitan cities. RESULTS: Of the 6234 evaluable patients, 5318 patients completed 2 years in the study. Microvascular complications were observed in 17.6% of patients (1096/6234); macrovascular complications were observed in 3.1% of patients (195/6234). Higher number of microvascular complications were noted in patients from non-metropolitan than in metropolitan cities (p < .0001). In 2 years, an improvement of 0.6% from baseline (8.1%) in mean glycated haemoglobin (HbA1c) was noted; 20.8% of patients met optimum glycaemic control (HbA1c < 7%). Hypertension (2679/3438, 77.9%) and dyslipidaemia (1776/3438, 51.7%) were the predominant CV risk factors in 2 years. The number of patients taking oral anti-diabetic drugs in combination with insulin increased in 2 years (baseline: 1498/6234 [24.0%] vs. 2 years: 1917/5763 [33.3%]). While biguanides and sulfonylureas were the most commonly prescribed, there was an evident increase in the use of dipeptidyl peptidase-IV inhibitors (baseline: 3049/6234, 48.9% vs. 2 years: 3526/5763, 61.2%). CONCLUSION: This longitudinal study represents the control of T2DM, its management and development of complications in Indian population. CLINICAL TRIAL REGISTRATION NUMBER: CTRI/2017/05/008452.

SGLT2i as a First-line Antihyperglycemic in the Management of Type 2 Diabetes in the Context of Indians: A Systematic Review and Consensus.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been used for almost a decade and have proven to be effective not only in managing Type 2 diabetes (T2D), but their cardio and renal protective features make them very useful in managing patients with risk of multiple comorbidities. This systematic review was undertaken by the authors because there is no evidence currently available in India that has studied the suitability of SGLT2i as a first-line agent in patients newly diagnosed with T2D in India. MATERIALS AND METHODS: First, literature was searched to identify features that are considered important when deciding on a first-line agent for managing T2D. A total of 5 broad topics were identified-glycemic control, extra glycemic effects, antihyperglycemic combination therapy, safety, and cost-effectiveness. These domains had further subheadings, and a total of 16 domains were identified. Metformin is the drug of choice as a first-line agent in such situations and has been considered the gold standard for evaluating the effects of SGLT2i across these domains. A systematic literature review on each domain was conducted to compare SGLT2i with the gold standard in Indian patients newly diagnosed with T2D. Evidence was graded (levels of evidence (LoE)-A, B, and C), and recommendations (class of recommendation (CoR)-I, II, and III) were classified by the expert group as defined in the methodology. RESULTS: According to the systematic reviews conducted, 11 domains had Level A evidence, 2 domains (impact on lipids and gut microbiome) had Level B, and 3 domains had Level C (ß-cell function, renal protection, and glycemic variability) evidence. Based on evidence and expert opinion, the authors recommend SGLT2i as a first-line agent for managing newly diagnosed patients with T2D with a Class I recommendation for 13 domains and Class II for the remaining 3 (impact on lipids, gut microbiome, and ß-cell function). Although a poorer level of evidence (Level C) was available for the glycemic variability domain, the authors still reported this as Class I recommendations according to their expert opinion and consensus. CONCLUSION: This article advocates adopting SGLT2 inhibitors as the primary treatment choice for treating patients with newly diagnosed T2D in India.

Estimating the total incidence of type 1 diabetes in children and adolescents aged 0-19 years from 1990 to 2050: a global simulation-based analysis.

BACKGROUND: Previous studies of type 1 diabetes in childhood and adolescence have found large variations in reported incidence around the world. However, it is unclear whether these reported incidence levels are impacted by differences in country health systems and possible underdiagnosis and if so, to what degree. The aim of this study was to estimate both the total and diagnosed incidence of type 1 diabetes globally and to project childhood type 1 diabetes incidence indicators from 1990 to 2050 for each country. METHODS: We developed the type 1 diabetes global microsimulation model to simulate the natural history and diagnosis of type 1 diabetes for children and adolescents (aged 0-19 years) in 200 countries and territories, accounting for variability in underlying incidence and health system performance. The model follows an open population of children and adolescents in monthly intervals and simulates type 1 diabetes incidence and progression, as well as health system factors which influence diagnosis. We calibrated the model to published data on type 1 diabetes incidence, autoantibody profiles, and proportion of cases diagnosed with diabetic ketoacidosis from 1990 to 2020 and assessed the predictive accuracy using a randomly sampled test set of data withheld from calibration. FINDINGS: We estimate that in 2021 there were 355 900 (95% UI 334 200-377 300) total new cases of type 1 diabetes globally among children and adolescents, of which 56% (200 400 cases, 95% UI 180 600-219 500) were diagnosed. Estimated underdiagnosis varies substantially by region, with over 95% of new cases diagnosed in Australia and New Zealand, western and northern Europe, and North America, but less than 35% of new cases diagnosed in west Africa, south and southeastern Asia, and Melanesia. The total number of incident childhood cases of type 1 diabetes is projected to increase to 476 700 (95% UI 449 500-504 300) in 2050. INTERPRETATION: Our research indicates that the total global incidence of childhood and adolescent type 1 diabetes is larger than previously estimated, with nearly one-in-two children currently undiagnosed. Policymakers should plan for adequate diagnostic and medical capacity to improve timely type 1 diabetes detection and treatment, particularly as incidence is projected to increase worldwide, with highest numbers of new cases in Africa. FUNDING: Novo Nordisk.

Indian Phenotype Characteristics Among Patients with Type 2 Diabetes Mellitus: Insights from a Non-interventional Nationwide Registry in India.

Background: Indian patients with type 2 diabetes mellitus (T2D) constitute one-sixth of affected adults globally. Here, we evaluate the association of body mass index (BMI) with body fat percentage (BF%) and glycated haemoglobin (HbA1c) levels among patients with T2D in India. Method: This was a cross-sectional Indian registry study across 845 geographically diverse zones between December 2017 and August 2019. Results: Of 37,927 patients, 55.6% were men, with a mean ± standard deviation age of 54.2 ± 11.5 years and HbA1c of 8.3 ± 1.71%. Mean ± standard deviation BMI and BF% were 27.0 ± 4.6 kg/m2 and 32.0 ± 8.0%, respectively. Overall, 15.4% of patients were overweight, and 25.0% were obese. Despite fewer males (20.7%) having BMI-based obesity than females (31.2%), around three-quarters of both sexes had BF%-defined obesity (males 77.2%; females 71.2%). One-third of males (34.6%) and 41.9% of females had BF%-defined obesity despite normal BMI. The association was substantiated by a moderately significant correlation (r=0.51) between BMI and BF% in the overall population (p<0.0001). Conclusion: This pan-India registry presents a real-world reflection of the Asian Indian phenotype: high BF% despite lower BMI in people with T2D. This highlights the importance of primordial and primary prevention, and may guide decisions on the choice of agents for glycaemic control, with a preference for drugs that promote weight loss or are weight neutral.

Twenty Years of Insulin Gla-100: A Systematic Evaluation of Its Efficacy and Safety in Type 2 Diabetes Mellitus.

INTRODUCTION: This systematic review aims to present the current evidence base with respect to the initiation and intensification of insulin therapy with glargine 100 U/mL (Gla-100) compared to other insulins in people with type 2 diabetes mellitus (T2DM). METHODS: A systematic literature search of PubMed (MEDLINE), EMBASE, and the Cochrane Central Register of controlled clinical trials databases was performed to identify studies published up to September 30, 2020 that compared the effects of Gla-100 to that of other insulin regimens in people with T2DM. Relevant information pertaining to the predefined outcomes of interest was extracted. Glycated hemoglobin (HbA1c) change and response rates along with overall hypoglycemia incidence were the primary efficacy and safety outcomes of interest. RESULTS: Seventy-nine studies (63 interventional and 16 non-interventional) in which Gla-100 was either initiated in previously insulin-naïve patients (n = 57) or used in an intensified regimen (n = 22) were identified and evaluated. In insulin-naïve patients, most studies demonstrated that Gla-100 was significantly better compared with premixed insulins and similar compared with neutral protamine Hagedorn (NPH) insulin, second-generation basal insulins, co-formulations, and other first-generation basal insulins in terms of the primary efficacy parameters. Overall hypoglycemia risk with Gla-100 was significantly lower compared with NPH, premixed, coformulation, and other first-generation basal insulins and significantly higher compared with second-generation basal insulins. In studies with intensified regimens, efficacy outcomes with Gla-100 were significantly better compared with insulin detemir (IDet); similar compared with NPH, second-generation basal insulins, co-formulations; and with premixed insulins. In these studies, overall hypoglycemia risk with Gla-100 was significantly lower compared with IDet and comparable to NPH, premixed insulins, co-formulations, and second-generation basal insulins. In addition, most intensification studies also revealed a significantly lower risk of nocturnal hypoglycemia with Gla-100-based regimens versus NPH and premixed insulins and a significantly greater risk compared to second-generation basal insulins. CONCLUSIONS: The evidence presented in this review suggests that Gla-100 is an effective option for both insulin initiation and intensification strategies used in the management of T2DM.

Efficacy and Safety of Insulin Glargine 300 U/mL in People with Type 2 Diabetes Uncontrolled on Basal Insulin: The 26-Week Interventional, Single-Arm ARTEMIS-DM Study.

INTRODUCTION: The efficacy and safety of switching to insulin glargine 300 U/mL (Gla-300) in type 2 diabetes mellitus (T2DM) uncontrolled on basal insulin (BI) has been demonstrated in the North American and Western European populations; however, there is limited data from other geographical regions with different ethnicities. The ARTEMIS-DM study aimed to evaluate the efficacy and safety of Gla-300 in people with T2DM uncontrolled on BI from Asia, Latin America and Middle East Africa. METHODS: The ARTEMIS-DM was a 26-week, prospective, interventional, single-arm, phase IV study (NCT03760991). Adults with T2DM previously uncontrolled (glycated haemoglobin [HbA1c] 7.5-10%) on BI were switched to Gla-300. The primary endpoint was change in HbA1c from baseline to 26 weeks. Key secondary endpoints were changes in HbA1c (week 12), fasting plasma glucose (FPG), self-monitored plasma glucose (SMPG) and BI dose from baseline to week 26. The safety and tolerability of Gla-300 were also assessed. RESULTS: A total of 372 (50% male) participants were included, with mean (standard deviation [SD]) age 60.9 (10.0) years, duration of diabetes 13.11 (7.48) years and baseline HbA1c 8.67 (0.77)% (71.22 [8.44] mmol/mol). A total of 222 (59.7%) participants were using insulin glargine 100 U/mL and 107 (28.8%) were using neutral protamine Hagedorn insulin as previous BI. There were clinically significant reductions in mean HbA1c (- 0.82%; primary endpoint), FPG and SMPG levels at week 26. With a pre-defined titration algorithm, mean Gla-300 dose increased from 27.48 U (0.35 U/kg) at baseline to 39.01 U (0.50 U/kg) at week 26. Hypoglycaemia events occurred in 20.4% of the participants; 1 (0.3%) participant had a severe hypoglycaemia event. CONCLUSION: In people with T2DM uncontrolled on previous BI, switching to Gla-300 with optimal titration guided by an algorithm was associated with improved glycaemic control and low incidence of hypoglycaemia across multiple geographic regions. GOV IDENTIFIER: NCT03760991.

Indian Reality of Clinical Practice and Patient Profile in Diabetes Care: Lessons from the IMPACT survey.

India shoulders a heavy burden of diabetes mellitus (DM), the management of which is suboptimal globally.& Objectives: Insulin Management: Practical Aspects in Choice of Therapy (IMPACT) survey was designed to gain insight into the ground (in-clinic) reality of DM management by physicians in India. METHODS: A survey consisting of 12 multiple-choice questions was conducted by SurveyMonkey® , focusing on practice profile, patient profile, and other aspects of DM management. RESULTS: The survey included 2424 physicians. Majority of them were general physicians (58.5%) followed by diabetologists (31.1%). Most (49.2%) of the respondents specified that the ideal time for a DM consultation is 15 min. However, 73.4% of them provided consultation of <10& min because of heavy patient load. Nearly half of the respondents reported that their patients consumed a diet with carbohydrate content of 60% to 80%, and 79.4% of them admitted that <50% of their patients adhered to dietary advice. About 73.5% of the respondents believed controlling fasting plasma glucose (FPG) level alone would not adequately control postprandial plasma glucose (PPG) level, and 93.0% of them preferred an insulin therapy at the initiation that controls both FPG and PPG levels. CONCLUSION: Limited consultation time, high-carbohydrate diet, and a need for choosing insulin regimens that provide control for both PPG and FPG levels are some ground realities of DM management in India. These realities need to be factored in while choosing treatment options to achieve the desired glycemic control and improve the status of diabetes care.

One-year trends from the LANDMARC trial: A 3-year, pan-India, prospective, longitudinal study on the management and real-world outcomes of type 2 diabetes mellitus.

INTRODUCTION: Longitudinal data on management and progression of type 2 diabetes mellitus (T2DM) in India are scarce. LANDMARC (CTRI/2017/05/008452), first-of-its-kind, pan-India, prospective, observational study aimed to evaluate real-world patterns and management of T2DM over 3 years. METHODS: Adults (≥25 to ≤60 years old at T2DM diagnosis; diabetes duration ≥2 years at enrolment; controlled/uncontrolled on ≥2 anti-diabetic agents) were enrolled. The first-year trends for glycaemic control, therapy and diabetic complications, including those from metropolitan and non-metropolitan cities are reported here. RESULTS: Of 6236 enrolled participants, 5654 completed 1 year in the study. Although the overall mean glycated haemoglobin (HbA1c) improved by 0.5% (baseline: 8.1%) at 1 year, only 20% of the participants achieved HbA1c <7%. Participants from metropolitan and non- metropolitan cities showed similar decrease in glycaemic levels (mean change in HbA1c: -0.5% vs. -0.5%; p = .8613). Among diabetic complications, neuropathy was the predominant complication (815/6236, 13.1% participants). Microvascular complications (neuropathy, nephropathy and retinopathy) were significantly (p < .0001) higher in non-metropolitan than metropolitan cities. Hypertension (2623/6236, 78.2%) and dyslipidaemia (1696/6236, 50.6%) continued to be the most commonly reported cardiovascular risks at 1 year. After 1 year, majority of the participants were taking only oral anti-diabetic drugs (OADs) (baseline: 4642/6236 [74.4%]; 1 year: 4045/6013 [67.3%]), while the proportion of those taking insulin along with OADs increased (baseline: 1498/6236 [24.0%] vs. 1 year: 1844/6013 [30.7%]). Biguanides and sulfonylureas were the most used OADs. The highest increase in use was seen for dipeptidyl peptidase-IV inhibitors (baseline: 3047/6236 [48.9%]; 1 year: 3529/6013 [58.7%]). Improvement in all glycaemic parameters was significantly (p < .0001) higher in the insulin vs. the insulin-naïve subgroups; in the insulin-naïve subgroup, no statistical difference was noted in those who received >3 vs. ≤3 OADs. CONCLUSIONS: First-year trends of the LANDMARC study offer insights into real-world disease progression, suggesting the need for controlling risk factors and timely treatment intensification in people with T2DM.

Efficacy of a Combination of Metformin and Vildagliptin in Comparison to Metformin Alone in Type 2 Diabetes Mellitus: A Multicentre, Retrospective, Real-World Evidence Study.

BACKGROUND: Early use of combination therapy in diabetes patients may lead to sustained glycemic control and thereby reduce the progression of diabetic complications. Given the limitation of the traditional stepwise intensification strategy, early combination therapy can be an effective approach. Therefore, this study aims to assess the real-world efficacy of a combination of metformin and vildagliptin in comparison to metformin alone in type 2 diabetes mellitus (T2DM) patients in India. METHODS: This was an observational, retrospective, non-interventional study based on electronic medical records (EMRs) of 2740 T2DM patients, retrieved from 2010 onwards from 22 diabetes centres across India. Adult drug naïve patients with a 5-year history of T2DM treated with either metformin or a combination of metformin and vildagliptin for at least 3 months were considered for this study. Efficacy assessment was done to evaluate the post-treatment HbA1c levels and patients requiring additional oral antidiabetic drugs (OADs) at the time of follow-up visit. Patients were also analyzed for the occurrence of adverse events. RESULTS: Out of the total, 2452 patients were in metformin only arm, and 288 patients were in metformin plus vildagliptin treatment arm. A more significant reduction in HbA1c level was observed in metformin plus vildagliptin arm than metformin only arm (median: -0.5% vs 0%, respectively; p<0.001). Patients requiring additional OAD at follow-up were significantly lesser in the metformin plus vildagliptin arm than the metformin only arm (15.6% vs 35.2%, respectively; p<0.001). The adverse events were comparable across the two arms, and commonly reported adverse events were giddiness, fatigue and gastric discomfort. CONCLUSION: The findings of this EMR-based real-world study emphasizes the need for early initiation of combination therapy (metformin plus vildagliptin) over metformin monotherapy for achieving better glycemic control.

Baseline characteristics of participants in the LANDMARC trial: A 3-year, pan-india, prospective, longitudinal study to assess management and real-world outcomes of diabetes mellitus.

INTRODUCTION: Longitudinal data on progression, complications, and management of type 2 diabetes mellitus (T2DM) across India are scarce. LANDMARC (CTRI/2017/05/008452), the first pan-India, longitudinal, prospective, observational study, aims to understand the management and real-world outcomes of T2DM over 3 years. METHODS: Adults (≥25 to ≤60 years old at T2DM diagnosis; diabetes duration ≥2 years at enrollment; controlled/uncontrolled on ≥2 anti-diabetic agents) were enrolled. Baseline characteristics were analyzed using descriptive statistics. RESULTS: Of the 6279 recruited participants, 6236 were eligible for baseline assessment (56.6% [n/N = 3528/6236] men; mean ± SD age: 52.1 ± 9.2 years, diabetes duration: 8.6 ± 5.6 years). mean ± SD HbA1c, fasting plasma glucose, and postprandial glucose values were 64 ± 17 mmol/mol (8.1 ± 1.6%), 142.8 ± 50.4 mg/dl, and 205.7 ± 72.3 mg/dl, respectively. Only 25.1% (n/N = 1122/6236) participants had controlled glycemia (HbA1c < 53 mmol/mol, <7%). Macrovascular and microvascular complications were prevalent in 2.3% (n/N = 145/6236) and 14.5% (n/N = 902/6236) participants, respectively. Among those with complications, non-fatal myocardial infarction (n/N = 74/145, 51.0%) and neuropathy (n/N = 737/902, 81.7%) were the most reported macrovascular and microvascular complication, respectively. Hypertension (n/N = 2566/3281, 78.2%) and dyslipidemia (n/N = 1635/3281, 49.8%) were the most reported cardiovascular risks. Majority (74.5%; n/N = 4643/6236) were taking oral anti-diabetic drugs (OADs) only, while 24.4% (n/N = 1522/6236) participants were taking OADs+insulin. Biguanides (n/N = 5796/6236, 92.9%) and sulfonylureas (n/N = 4757/6236, 76.3%) were the most reported OADs. Basal (n/N = 837/6236, 13.4%) and premix (n/N = 684/6236, 11.0%) insulins were the most reported insulins. CONCLUSIONS: Baseline data from LANDMARC help understand the clinical/medical profile of study participants and underscore the extent of suboptimal glycemic control and prevalence of associated complications in a vast majority of Indians with T2DM.

Effect of Gliclazide or Gliclazide plus Metformin Combination on Glycemic Control in Patients with T2DM in India: A Real-World, Retrospective, Longitudinal, Observational Study from Electronic Medical Records.

BACKGROUND: The efficacy of gliclazide has been reported in clinical trials in India. However, real-world data on the effectiveness of gliclazide in India is unavailable. OBJECTIVE: To provide real-world evidence regarding the effectiveness of gliclazide or gliclazide + metformin fixed-dose combination or separate medications, used either as monotherapy or as the latest add-on to other antihyperglycemic agents in reducing glycated hemoglobin (HbA1c) levels in Indian patients with type 2 diabetes mellitus (T2DM). METHODS: Electronic medical record data of adult patients who were diagnosed with T2DM who were newly initiated on or had been prescribed gliclazide or gliclazide + metformin combination for < 30 days as monotherapy or as add-on therapy to other antihyperglycemic agents, and had HbA1c ≥ 6.5% were retrospectively analyzed. Mean change in HbA1c from baseline was the primary endpoint. Secondary endpoints were assessment of dosages and formulations of gliclazide or gliclazide + metformin prescribed in the HbA1c spectrum and antihyperglycemic agents to which gliclazide or gliclazide + metformin was added as an adjunct. Readings were obtained before initiating gliclazide or gliclazide + metformin and after at least 90 days of treatment with gliclazide or gliclazide + metformin. RESULTS: Included patients (n = 498) were categorized into gliclazide only (n = 66), gliclazide + metformin only (n = 179), gliclazide add-on (n = 169), and gliclazide + metformin add-on (n = 84) groups. Mean (95% confidence interval [CI]) change in HbA1c among patients with baseline HbA1c > 7% was - 0.8% (- 1.26, - 0.34) in gliclazide only group; - 1.6% (- 1.89, - 1.31; p < 0.001) in gliclazide + metformin group; - 1.2% (- 1.50, - 0.90; p < 0.001) in add-on gliclazide group; and - 1.4% (- 1.75, - 1.05; p < 0.001) in add-on gliclazide + metformin group. Gliclazide once daily was the most prescribed regimen in the gliclazide only group (72.7%), with 60 mg being the most prescribed modified-release dose (62.5%). Gliclazide + metformin twice daily was the most prescribed regimen in the gliclazide + metformin group (69.3%) with 80 mg + 500 mg being the most prescribed immediate-release dose (62.9%). Gliclazide and gliclazide + metformin were most added as an adjunct to existing prescriptions of biguanides (83.4%) or insulin (64.3%), respectively. CONCLUSION: Gliclazide or gliclazide + metformin prescribed as mono- or add-on therapy during routine clinical practice effectively reduced HbA1c in Indian patients with T2DM, thus validating the use of gliclazide and gliclazide + metformin for managing T2DM in India.

A Practitioner's Toolkit for Insulin Motivation in Adults with Type 1 and Type 2 Diabetes Mellitus: Evidence-Based Recommendations from an International Expert Panel.

AIM: To develop an evidence-based expert group opinion on the role of insulin motivation to overcome insulin distress during different stages of insulin therapy and to propose a practitioner's toolkit for insulin motivation in the management of diabetes mellitus (DM). BACKGROUND: Insulin distress, an emotional response of the patient to the suggested use of insulin, acts as a major barrier to insulin therapy in the management of DM. Addressing patient-, physician- and drug-related factors is important to overcome insulin distress. Strengthening of communication between physicians and patients with diabetes and enhancing the patients' coping skills are prerequisites to create a sense of comfort with the use of insulin. Insulin motivation is key to achieving targeted goals in diabetes care. A group of endocrinologists came together at an international meeting held in India to develop tool kits that would aid a practitioner in implementing insulin motivation strategies at different stages of the journey through insulin therapy, including pre-initiation, initiation, titration and intensification. During the meeting, emphasis was placed on the challenges and limitations faced by both physicians and patients with diabetes during each stage of the journey through insulinization. REVIEW RESULTS: After review of evidence and discussions, the expert group provided recommendations on strategies for improved insulin acceptance, empowering behavior change in patients with DM, approaches for motivating patients to initiate and maintain insulin therapy and best practices for insulin motivation at the pre-initiation, initiation, titration and intensification stages of insulin therapy. CONCLUSIONS: In the management of DM, bringing in positive behavioral change by motivating the patient to improve treatment adherence helps overcome insulin distress and achieve treatment goals.

Blood Pressure Variability in Patients with Diabetes Mellitus with Hypertension: Treatment Recommendations and Role of Amlodipine.

Recently, blood pressure variability (BPV) has gained focus owing to its role in predicting cardiovascular (CV) outcomes. Additionally, alterations in BPV contribute to the progression of end organ damage and trigger vascular events in hypertensive patients. Therefore, amelioration of BPV is considered a potentially important target and different classes of drugs are used to achieve the desired blood pressure (BP) goal. Based on several studies and clinical trials, treatments with CCB such as amlodipine have been found to be most effective in the management of BPV in hypertensive patients with diabetes. Growing evidence substantiates the role of amlodipine in significant reduction of BPV, thus, lowering the risk of diabetes related complications. This review sheds light on the importance of BPV reduction and the effectiveness of amlodipine in preventing cardiovascular morbidity and mortality in hypertensive patients with diabetes.

The Thyroid Registry: Clinical and Hormonal Characteristics of Adult Indian Patients with Hypothyroidism.

OBJECTIVES: Appropriate treatment of hypothyroidism requires accurate diagnosis. This registry aimed to study the disease profile and treatment paradigm in hypothyroid patients in India. MATERIALS AND METHODS: We registered 1500 newly diagnosed, treatment-naïve, adult hypothyroid males and nonpregnant females across 33 centers and collected relevant data from medical records. The first analysis report on baseline data is presented here. RESULTS: The mean age of the study population was 41.1 ± 14.01 years with a female to male ratio of 7:3. The most frequently reported symptoms and signs were fatigue (60.17%) and weight gain with poor appetite (36.22%). Menstrual abnormalities were reported in all women (n = 730) who had not attained menopause. Grades 1 and 2 goiter (as per the WHO) were observed in 15.41% and 3.27% patients, respectively. Comorbidities were reported in 545 patients (36.36%), type 2 diabetes mellitus being the most prevalent (13.54%) followed by hypertension (11.34%). Total serum thyroxine (T4) and thyroid-stimulating hormone (TSH) levels were assessed in 291 (19.47%) patients only. In majority of patients (81%), treatment was based on serum TSH levels alone. The dose of levothyroxine ranged from 12.5 to 375 mcg. CONCLUSIONS: Guidelines suggest a diagnosis of hypothyroidism based on TSH and T4 levels. However, most of the patients as observed in this registry received treatment with levothyroxine based on TSH levels alone, thus highlighting the need for awareness and scientific education among clinicians in India. The use of standard doses (100, 75, and 25 mcg) of levothyroxine may point toward empirical management practices.

Efficacy and Safety of IDegLira in Participants with Type 2 Diabetes in India Uncontrolled on Oral Antidiabetic Drugs and Basal Insulin: Data from the DUAL Clinical Trial Program.

INTRODUCTION: The efficacy and safety of insulin degludec/liraglutide (IDegLira) has been evaluated in the Dual Action of Liraglutide and Insulin Degludec in Type 2 Diabetes (DUAL) phase 3 clinical trial program. In this post hoc analysis, we compared the efficacy and safety of IDegLira in the Indian subpopulation with the results from the global trial population of DUAL trials. The analysis includes participants uncontrolled on oral antidiabetic drugs (OADs) in DUAL I and DUAL IV and participants uncontrolled on basal insulin and OADs in DUAL II. METHODS: Three phase 3 trials were included in the analysis: DUAL I extension (IDegLira vs. insulin degludec or liraglutide 1.8 mg in participants uncontrolled on metformin ± pioglitazone; 52 weeks; n = 1663), DUAL IV (IDegLira vs. placebo as an add-on to a regimen of sulfonylurea ± metformin; 26 weeks; n = 435) and DUAL II (IDegLira vs. insulin degludec in participants uncontrolled on basal insulin + OADs; 26 weeks; n = 398). There were 251, 64 and 64 participants, respectively, at the Indian sites. RESULTS: In the Indian subpopulations, the reductions in glycated hemoglobin (HbA1c) with IDegLira were substantial [DUAL I: 1.96% (-21 mmol/mol); DUAL IV: -1.40% (-15 mmol/mol); DUAL II: -2.20% (-24 mmol/mol)] and significantly greater than those in the comparators in each trial. IDegLira was generally weight-neutral after the administration of OADs (-0.3 and +0.6 kg in DUAL I and DUAL IV) and resulted in weight loss after the administration of basal insulin (-2.1 kg in DUAL II). Hypoglycemia rates were 1.98, 1.08 and 0.37 events/patient-years of exposure (PYE) for IDegLira, insulin degludec and liraglutide in DUAL I, 4.06 and 0.36 events/PYE for IDegLira and placebo in DUAL IV and 1.16 and 0.83 events/PYE with IDegLira and insulin degludec in DUAL II. CONCLUSIONS: Results from the Indian subpopulations reflect those of the global study populations, supporting IDegLira as an effective and safe treatment option for people with type 2 diabetes inadequately controlled on OADs or basal insulin + OADs in the South Asian population. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01336023 (DUAL I), NCT01392573 (DUAL II), NCT01618162 (DUAL IV). FUNDING: Novo Nordisk A/S, Bagsvaerd, Denmark.