COVID-19 and Diabetes.

The prevalence of diabetes in people with coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has varied worldwide. Most of the available evidence suggests a significant increase in severity and mortality of COVID-19 in people with either type 1 (T1DM) or type 2 diabetes mellitus (T2DM), especially in association with poor glycemic control. While new-onset hyperglycemia and new-onset diabetes (both T1DM and T2DM) have been increasingly recognized in the context of COVID-19 and have been associated with worse outcome, no conclusive evidence yet suggests direct tropism of SARS-CoV-2 on the ß cells of pancreatic islets. While all approved oral antidiabetic agents appear to be safe in people with T2DM having COVID-19, no conclusive data are yet available to indicate a mortality benefit with any class of these drugs, in the absence of large randomized controlled trials.

Cardiovascular and Renal Outcomes With Sodium-Glucose Cotransporter-2 Inhibitors and Dipeptidyl Peptidase-4 Inhibitors Combination Therapy: A Meta-Analysis of Randomized Cardiovascular Outcome Trials.

OBJECTIVE: The cardiovascular (CV) and renal benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in people with type 2 diabetes are well known. However, similar beneficial effects of SGLT2i in combination with dipeptidyl peptidase-4 inhibitors (DPP4i) are unknown. It is of interest to explore a trial-level meta-analysis to fill this knowledge gap. METHODS: A literature search was conducted in the PubMed and Embase databases until January 31, 2023. All CV outcome trials (CVOTs) reporting the CV and renal outcomes of SGLT2i with or without background DPP4i therapy against the placebo were retrieved. A meta-analysis was subsequently conducted by applying the inverse variance-weighted averages of pooled logarithmic hazard ratio using primarily random-effects analysis. RESULTS: This meta-analysis showed that the beneficial 3-point major adverse cardiovascular events composite (3 CVOTs; N = 32 418), the composite of CV death or heart failure hospitalization (hHF) (4 CVOTs; N = 37 687), hHF (3 CVOTs; N = 27 545), CV death (4 CVOTs; N = 34 565), and renal outcomes (2 CVOTs; N = 25 406) with SGLT2i were similar with or without background DPP4i therapy against the placebo (Pheterogeneity = .71, .07, .87, .72, and .25; respectively). However, against the placebo, the summary estimates for the 3-point major adverse cardiovascular events composite, hHF, and renal outcomes were stronger with SGLT2i alone, whereas the summary estimates for CV death or hHF composite were larger with SGLT2i with background DPP4i therapy. CONCLUSION: Beneficial CV and renal effects of SGLT2i are similar against the placebo regardless of background DPP4i therapy.

Role and Significance of Dietary Protein in the Management of Type 2 Diabetes and Its Complications in India: An Expert Opinion.

BACKGROUND: Obesity, prediabetes, and type 2 diabetes mellitus (T2DM) pose a triple burden in India. Almost two-thirds of people with diabetes (PWD) in India are found to have suboptimal glycemic, blood pressure, and lipid control. Medical nutrition therapy (MNT) in diabetes has emphasized on the amount and type of carbohydrates for years. However, protein, an important macronutrient in diabetes management, needs to be focused upon, especially in India, where the consumption is found to be lower than the recommendations provided by most guidelines. AIM: An expert committee attempted to review the role of dietary protein in the management of T2DM, arrive at a consensus on the significance of increasing dietary protein for various benefits, and offer practical guidance on ways to improve protein intake among Indians. METHODOLOGY: A total of 10 endocrinologists and diabetologists, one nephrologist, and three registered dietitians representing four zones of India formed the expert committee. An in-depth review of literature in the Indian context was carried out, and the draft document was shared with the expert committee, and their views were incorporated into the same. The expert committee then assembled virtually to deliberate on various aspects of the role of protein in T2DM management. The experts from various specialties gave their valuable inputs and suggestions from their extensive personal clinical experience and research work, which helped to reach a consensus on the role and significance of protein in the management of T2DM and its complications in India. RESULTS: There is abundant evidence that MNT is essential for the prevention and management of T2DM and its complications. Experts agreed that increasing protein intake offers myriad health benefits, namely reducing glycemic variability, improving glycemic control, increasing insulin sensitivity, improvement in lipid profile and immunity, and helping in weight management and preservation of muscle mass in PWD. The expert committee suggested aiming for an increase in protein intake by at least 5-10% of the current intake in lieu of carbohydrates in PWD. Experts also highlighted the need for more data quantifying the unmet protein needs in the Indian PWD, especially among vegetarians. Randomized controlled trials to study the effect of protein in diabetes complications such as cardiovascular disease (CVD) and diabetic kidney disease (DKD) and comorbid conditions such as sarcopenia among the Indian population are also warranted. CONCLUSION: Increasing protein quantity and quality in the diets of Indian PWD could significantly contribute to positive health outcomes. Increased protein intake, preferably through dietary sources to meet the requirements and, when required using diabetes-specific protein supplements (DSPS), is recommended in the prevention and control of T2DM.

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.

Management of Hyperglycemia in COVID-19 and Post-COVID-19 Syndrome - Proposed Guidelines for India.

SARS-CoV-2 virus spread rapidly all over the globe in 2020 and the second wave has taken our nation, India by storm. The pandemic has posed unique challenges in people with metabolic disorders, including diabetes, hypertension, obesity, pulmonary, cardiovascular, kidney and non-alcoholic fatty liver disease. Uncontrolled diabetes, in conjunction with endocrine, inflammatory and metabolic effects of the infection itself has made management of hyperglycemia in COVID-19 infection particularly challenging. Furthermore, the post-COVID-19 syndrome has also emerged as a sequela in COVID-19 survivors, increasing the risk of death, complications and adding further burden on the health care system. With more than a year of experience, we have gained substantial insight; and now provide practical recommendations on the management of hyperglycemia in COVID-19 as well as post COVID-19 syndrome.

Expert Group Recommendations on Detection and Management of Hypoglycemia in Routine Clinical Practice in Insulin Treated Patients with Diabetes.

Hypoglycemia is a key barrier to optimum glycemic control in insulin treated diabetes patients. A national level expert group meeting was held at the 11th national insulin summit to analyze published data from clinical studies and guidelines to evolve consensus recommendations on identification and management of hypoglycemia in insulin-treated diabetes patients. This consensus statement emphasizes consideration of suggestive symptoms or blood glucose levels ≤70 mg/dl and ability to self-treat in identification and classification of hypoglycemia. Patient questionnaire administration at each patient visit will enable accurate reporting of hypoglycemia. Patients with strict glycemic control, high glycemic variability, history of severe hypoglycemia, impaired hypoglycemia awareness, long duration of disease or insulin therapy could be at an increased risk of hypoglycemia. Prevention of hypoglycemia should include monitoring and goal setting, patient education, dietary intervention, exercise counseling and medication adjustment. Basal insulin analogues (vs. NPH), rapid-acting insulin analogues (vs. RHI) and premix insulin analogues (vs. BHI) are more appropriate options with superiority of insulin degludec to insulin glargine U100 and IDegAsp to BIAsp 30 to reduce the risk of hypoglycemia. This consensus statement provides practical guidance for physicians in effectively managing and minimizing the risk of hypoglycemia in insulin treated diabetes patients.

Consensus on "Basal insulin in the management of Type 2 Diabetes: Which, When and How?"

INTRODUCTION: Type 2 diabetes mellitus (T2DM) has attained epidemic proportions and continues to increase despite the availability of a number of oral antidiabetic medications and major advances made in insulin delivery since its discovery nearly a hundred years ago. One, amongst many other reasons responsible for the inability to achieve adequate glycaemic control in a substantial proportion of T2DM patients is the delayed initiation and inappropriate intensification of insulin treatment. Appropriate initiation and intensification of insulin is critical for the successful achievement of tight glycaemic control. OBJECTIVE: To provide simple and easily implementable guidelines to primary care physicians on basal insulin initiation and intensification, along with use of basal insulin in special situations (hepatic failure, renal failure and gestational diabetes mellitus). METHODS: Each consensus statement on basal insulin initiation, intensification and use of basal insulin in special situations was evaluated for dosing and titration based on established guidelines, data from approved pack inserts, prescribing information or summary of product characteristics for each insulin type, and published scientific literature. These evaluations were then factored into the national context based not only on the clinical experience of the expert committee representatives' but also based on the common therapeutic practices followed in India to successfully achieve optimal glucose control. RESULTS: Recommendations on initiation and intensification of basal insulin, and its use in special situations, have been developed. The key recommendations are to initiate basal insulin when 2 or 3 oral antidiabetic medications fail to achieve target glycaemic control, or in symptomatic patients with glycated haemoglobin value greater than 9%. Depending upon patient characteristics, any of the four available basal insulins [Neutral protamine Hagedorn (NPH), Glargine (IGlar), Detemir (IDet), Degludec (IDeg)] can be used. However, IDeg has a longer duration of action, comparatively lesser hypoglycaemia (both overall and nocturnal) and more flexibility in administration timing compared to IGlar) and IDet. Inability to maintain glycaemic control should lead to prompt intensification of basal insulin treatment by adding mealtime insulin, consisting of one to three injections of either rapid-acting insulin analog or regular insulin; depending upon patient characteristics, intensification can also be achieved by transition from basal insulin to twice daily premixed insulin analogs/premixed human insulin/insulin co-formulations. IDeg/IDet can be used in all grades of renal and hepatic impairment; and IDet has been approved for use in gestational diabetes mellitus. CONCLUSIONS: We hope that these consensus based recommendations shall be a useful reference tool for health care practitioners and help them in initiating and intensifying insulin therapy in T2DM patients in order to achieve optimal glycaemic control.

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.

Review of Clinical Profile of IDegAsp.

In patients with diabetes, treatment intensification requires basal and bolus insulin injections to control the fasting and prandial insulin needs. To overcome the burden of multiple daily injections, co-formulating basal and bolus insulins in single injection could allow a simple regimen with fewer injections. Current premixed insulin analogues are limited by the protaminated insulin component, which cannot provide effective basal coverage. While, long-acting insulin analogues like insulin glargine and insulin detemir cannot be combined with rapid-acting insulin analogues due to physicochemical incompatibility. Insulin degludec/insulin aspart (IDegAsp) is a soluble co-formulation of two distinct insulin analogues in the ratio of 70% ultra-long-acting insulin degludec (IDeg) and 30% rapid-acting insulin aspart (IAsp). The distinct PK/PD properties of IDeg and IAsp components are preserved in the co-formulation, with the rapid absorption characteristics of IAsp and flat and stable profile of IDeg maintained separately. Size exclusion chromatography studies of IDegAsp indicate that IDeg and lAsp exist as stable di-hexamers and hexamers, respectively in the formulation. Moreover, at steady state, the prandial and basal glucose lowering effects of IDeg and IAsp were distinct and clearly separated. A clear dose-response relationship was observed in patients with type 1 and type 2 diabetes treated with IDegAsp. The glucose lowering effects of basal and prandial components of IDegAsp are maintained in elderly (≥ 65 years of age) patients with type 1 diabetes. In addition, the PK and clearance of IDeg and IAsp are not affected by mild, moderate or severe renal or hepatic impairment. Presence of two distinct insulin analogues, as a soluble co-formulation with basal component with an ultra-long duration of action makes IDegAsp an advance to premix insulins.

Efficacy and safety of oral semaglutide in type 2 diabetes: A systematic review of real-world evidence.

BACKGROUND AND AIMS: Oral semaglutide has undergone global Phase 3 development programs named PIONEER and approved for therapeutic use in people with type 2 diabetes (T2D). We aim to systematically review the efficacy and safety of oral semaglutide in real-world settings. METHODS: We systematically searched the electronic databases of PubMed, Google Scholar, and ClinicalTrials.gov from inception until March 15, 2024, using several keywords with Boolean "AND". We retrieved all the available granular details of real-world studies (RWS). RESULTS: To date, results from four prospective and ten retrospective real-world studies of oral semaglutide in T2D are available. In prospective studies, the primary outcome of HbA1c reduction varied from -0.9 % to -1.6 %, weight loss varied from -4.7 kg to -8.2 kg and HbA1c target of <7 % was achieved in 30 %-64 % with oral semaglutide. In retrospective studies, HbA1c reduction varied from -0.4 % to -1.8 %, weight reduction varied from -1.4 to -9.0 kg, HbA1c target of <7 % was achieved in 32-64 %, and 30-41 % of people with T2D had ≥5 % weight loss with oral semaglutide. Gastrointestinal adverse events with oral semaglutide varied from 16 % to 50 % in prospective and 6 %-47 % in retrospective RWS. Overall, 0 %-18 % of patients had oral semaglutide discontinuation due to any cause. CONCLUSION: Oral semaglutide exhibited a reasonable reduction in HbA1c and weight in people with T2D, consistent with the findings from PIONEER trials. While no new safety issues emerged, the inherent limitations of RWS underscore the necessity of long-term investigations to comprehensively assess safety.

An overview of therapeutic options of obesity management in India: the Integrated Diabetes and Endocrinology Academy (IDEA) 2023 Congress update.

INTRODUCTION: With newer anti-obesity medications (AOMs) being introduced at a rapid pace, it is prudent to make a concise and updated clinical practice document that may help busy clinicians in daily clinical practice. A group of metabolic physicians, diabetologists, endocrinologists, and bariatric surgeons assembled during the Integrated Diabetes and Endocrine Academy 2023 Congress (IDEACON, July 2023, Kolkata, India) to compile an update of pharmacotherapeutic options for managing people with obesity in India. AREAS COVERED: After an extensive review of the literature by experts in different domains, this update provides all available information on the management of obesity, with a special emphasis on both currently available and soon-to-be-available AOMs, in people with obesity. EXPERT OPINION: Several newer AOMs have been shown to reduce body weight significantly, thus poised to make a paradigm shift in the management of obesity. While the tolerability and key adverse events associated with these AOMs appear to be acceptable in randomized controlled trials, pharmacovigilance is vital in real-world settings, given the absence of sufficiently long-term studies. The easy availability and affordability of these drugs is another area of concern, especially in developing countries like India.

Insulin Access Enhancement in India: Expert Views on Integrating Interchangeable Biosimilar Insulin Glargine.

Achieving and maintaining optimal glycemic targets is the fundamental goal of the management of diabetes. However, failure of oral antidiabetic drugs (OADs) to sustain the targeted glycemic levels in individuals with progressing disease often requires initiation of insulin therapy. This article consolidates the expert opinions of 377 doctors who participated in 34 advisory board meetings held digitally (n=23) and in person (n=11) across India. The present report underscores the need for readily available alternatives, such as biosimilar insulins, in the Indian healthcare market to make insulin accessible to every patient with diabetes. The introduction of biosimilar insulins in the Indian healthcare market is the key to making insulin accessible to every patient with diabetes. Biosimilars are biologic products that closely resemble reference/originator biologics and demonstrate no clinically meaningful differences in safety and effectiveness. The concept of interchangeability serves as a pivotal differentiator for biosimilars, underlining their reliability and safety, and plays a significant role in their broader acceptance and integration into healthcare systems. The 'interchangeability' designation by the United States Food and Drug Administration (USFDA) elevates the biosimilar concept, promoting faster and broader adoption of insulin biosimilars, especially benefiting patients prone to non-adherence to insulin therapy. Healthcare providers are encouraged to consider the option of initiating or transitioning to biosimilar insulin glargine to address the insulin accessibility challenges.

Will lobeglitazone rival pioglitazone? A systematic review and critical appraisal.

BACKGROUND AND AIMS: Lobeglitazone (LGZ), a newly researched thiazolidinedione (TZD) thought to have lesser side effects compared with pioglitazone (PGZ), has been recently approved for the treatment of type 2 diabetes (T2D) in India. We aim to conduct an updated systematic review of LGZ to critically appraise its efficacy and safety in the context of PGZ. METHODS: A systematic literature search was carried out in the electronic database of PubMed until Jan 15, 2023, using specific keywords and MeSH terms. All studies which evaluated LGZ in people with T2D were retrieved and data were synthesized with regard to its efficacy and safety. A comparative critical appraisal was additionally made in the context of PGZ in T2D. RESULTS: Four randomized controlled, one prospective observational, and two real-world studies have evaluated the safety and efficacy of LGZ against placebo or active comparators either as monotherapy or in combination therapy. HbA1c reduction with LGZ 0.5 mg was superior to the placebo but similar to PGZ 15 mg and sitagliptin (SITA) 100 mg. Weight gain with LGZ was significantly higher compared to placebo and SITA but similar to PGZ. Edema was more frequently observed with LGZ compared to placebo, PGZ, and SITA. CONCLUSION: No substantial evidence is yet available that suggests LGZ could be a better alternative to PGZ both in the context of glycemic or extra-glycemic effects. At least in the short-term, adverse events of LGZ are indifferent from PGZ. More data is additionally needed to claim any advantage of LGZ over PGZ.

Efficacy and safety of imeglimin in type 2 diabetes: A systematic review and meta-analysis of randomized placebo-controlled trials.

BACKGROUND & AIMS: Imeglimin is a novel new oral compound recently approved for treating type 2 diabetes (T2D) in India. We conducted a systematic review and meta-analysis to evaluate the efficacy of imeglimin in people with T2D in the approved dose of 1000 mg twice daily (BID). METHODS: We systematically searched the database of PubMed until December 20, 2022, and retrieved all published double-blind, randomized, placebo-controlled trials (RCTs) conducted with imeglimin 1000 mg BID, using appropriate keywords and MeSH terms. A meta-analysis was conducted to study the HbA1c lowering effect of imeglimin 1000 mg BID in people with T2D using the Comprehensive meta-analysis (CMA) software Version 3, Biostat Inc. Englewood, NJ, USA. RESULTS: Of the seven Phase 2 studies and three Phase 3 studies conducted so far, only three published double-blind RCTs have reported the efficacy and safety of imeglimin 1000 mg BID against the placebo. Our meta-analysis using the random-effects model from two monotherapy studies (n = 360) showed imeglimin 1000 mg BID reduce HbA1c significantly (Δ -0.9%, 95% Confidence Interval [CI], -1.1 to -0.74%; P < 0.0001) against the placebo, without any heterogeneity (I2 = 0%). The pooled meta-analysis from all three RCTs (n = 574) found a significant reduction in HbA1c with imeglimin 1000 mg BID (Δ -0.79%; 95% CI, -1.00 to -0.59%; P < 0.0001) compared to placebo with high heterogeneity. CONCLUSIONS: This meta-analysis found a significant HbA1c lowering effect of imeglimin in people with T2D with an acceptable tolerability profile. Still, larger and longer studies are needed.

New-onset diabetes with sodium-glucose cotransporter-2 inhibitors in prediabetes: An updated meta-analysis and possible mechanisms.

BACKGROUND AND AIMS: A recent systematic review and meta-analysis studied the effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on new-onset diabetes (NOD) in adults with prediabetes having chronic kidney disease and heart failure. In light of other large randomized controlled trials (RCTs) of SGLT2i published after this meta-analysis that also reported the NOD outcome in adults with prediabetes, it is of interest to update the NOD outcome with SGLT2i. METHODS: A systemic search in the PubMed and Embase electronic database was made until March 31, 2023, using specific MeSH keywords following PRISMA protocol. Subsequently, we conducted a meta-analysis using the random effects model while applying the inverse variance-weighted averages of pooled logarithmic hazard ratio (HR). Heterogeneity was measured using Higgins I2 and Cochrane Q statistics and publication bias was evaluated by applying funnel plots. A sensitivity exclusion analysis was additionally made. RESULTS: This meta-analysis of five RCTs (N = 6752) found a significant reduction in NOD (HR 0.81; 95% CI, 0.69-0.94; P = 0.005) with SGLT2i in adults with prediabetes without any heterogeneity (I2 = 0%). CONCLUSIONS: SGLT2i has the potential to reduce NOD in adults with prediabetes. Since no effect on HbA1c reduction was seen in adults with prediabetes in all five RCTs included in this meta-analysis, it is conceivable that reduction in NOD is not related to the masking of blood glucose exerted by SGLT2i. However, only an adequately powered trial of SGLT2i in people with prediabetes with a sufficient wash-out period will confirm these findings.

Noninsulin-based antihyperglycemic medications in patients with diabetes and COVID-19: A systematic review and meta-analysis.

BACKGROUND: Patients with diabetes are more likely to suffer COVID-19 complications. Using noninsulin antihyperglycemic medications (AGMs) during COVID-19 infection has proved challenging. In this study, we evaluate different noninsulin AGMs in patients with COVID-19. METHODS: We searched Medline, Embase, Web of Science, and Cochrane on 24 January 2022. We used the following keywords (COVID-19) AND (diabetes mellitus) AND (antihyperglycemic agent). The inclusion criteria were studies reporting one or more of the outcomes. We excluded non-English articles, case reports, and literature reviews. Study outcomes were mortality, hospitalization, and intensive care unit (ICU) admission. RESULTS: The use of metformin rather than other glucose-lowering medications was associated with statistically significant lower mortality (risk ratio [RR]: 0.60, 95% confidence interval [CI]: 0.47, 0.77, p < .001). Dipeptidyl peptidase-4 inhibitor (DPP-4i) use was associated with statistically significantly higher hospitalization risk (RR: 1.44, 95% CI: 1.23, 1.68, p < .001) and higher risk of ICU admissions and/or mechanical ventilation vs nonusers (RR: 1.24, 95% CI: 1.04, 1.48, p < .02). There was a statistically significant decrease in hospitalization for SGLT-2i users vs nonusers (RR: 0.89, 95% CI: 0.84-0.95, p < .001). Glucagon-like peptide-1 receptor agonist (GLP-1RA) use was associated with a statistically significant decrease in mortality (RR: 0.56, 95% CI: 0.42, 073, p < 0.001), ICU admission, and/or mechanical ventilation (RR: 0.79, 95% CI: 0.69-0.89, p < .001), and hospitalization (RR: 0.73, 95% CI: 0.54, 0.98, p = .04). CONCLUSIONS: AGM use was not associated with increased mortality. However, metformin and GLP-1RA use reduced mortality risk statistically significantly. DPP-4i use was associated with a statistically significant increase in the risk of hospitalization and admission to the ICU.

Non-sugar sweeteners and health outcomes in adults without diabetes: deciphering the WHO recommendations in the Indian context.

BACKGROUND AND AIMS: A systematic review and meta-analysis conducted by the World Health Organization (WHO) assessed the health outcomes of non-sugar sweeteners (NSS) in randomized controlled trials (RCTs) and prospective cohort studies (PCSs) and reported conflicting findings. We aim to decipher these conflicting findings in RCTs and PCSs by critically reviewing their results, comparing them with previous meta-analyses, and providing a simplified interpretation including the Indian perspective. METHODS: We critically reviewed the 210-page dossier of WHO including the full text of most of the key studies of NSS included in this meta-analysis and subsequently compared it with previous meta-analyses to identify similarities and differences to address a few key questions pertaining to health outcomes associated with NSS use in adults. RESULTS: Poor health outcomes are often associated with excess sugar intake. While NSS are typically consumed as a sugar replacement, benefits are conflicting. While RCTs found some benefits in the short term, PCSs found harm associated with NSS use in the long term. CONCLUSION: The 2022 WHO meta-analysis that assessed the health outcomes of NSS is the most robust and critically analyzed document available to date. Despite the absence of any strong conclusion that suggests NSS consumption increases the risk of cardio-metabolic disorders, no firm evidence also rejects this statement. NSS could be an attractive replacement for sugar in overweight/obese people in the short term, but long-term harm cannot be fully ruled out. We suggest avoiding consuming sugar and restricting NSS intake wherever possible until long-term studies confirm or refute these findings.

Protein restriction in adults with chronic kidney disease, with or without diabetes: Integrated Diabetes and Endocrine Academy (IDEA) consensus statement for Indian patients.

BACKGROUND AND AIMS: Most guidelines recommend protein restriction in adults with chronic kidney disease (CKD), with or without diabetes. However, advising protein restriction for every person with CKD is controversial. We aim to arrive at a consensus on this topic, especially among Indian adults with CKD. METHODS: A systematic literature search in the PubMed electronic database was undertaken using specific keywords and MeSH terms until May 1, 2022. All the retrieved literature was circulated and rigorously deliberated upon by the panel members. RESULTS: Seventeen meta-analyses that evaluated the outcomes of protein restriction in adults with CKD, with or without diabetes, met our inclusion criteria and were analyzed. A low-protein diet (LPD) in people with stages 3-5 of CKD (who are not on haemodialysis [HD]) reduces the severity of uremic symptoms and the rate of decline in glomerular filtration rate, leading to a delay in dialysis initiation. However, LPD in patients on maintenance HD may not be desirable because HD-induced protein catabolism may lead to protein-energy malnutrition. Since the average protein intake among Indians is much lower than recommended, this must be taken into consideration before recommending LPD for all Indian adults with CKD, particularly those on maintenance HD. CONCLUSION: It is essential to assess the nutritional status of people with CKD, particularly in countries like India where average daily protein intake is poor, before recommending guideline-directed protein restriction. The prescribed diet, including the quantity and quality of proteins, should be tailored to the person's habits, tastes, and needs.

Diagnostic approach in 46, XY DSD: an endocrine society of bengal (ESB) consensus statement.

OBJECTIVES: 46, XY difference/disorder of sex development (DSD) is a relatively uncommon group of heterogeneous disorders with varying degree of underandrogenization of male genitalia. Such patients should be approached systematically to reach an aetiological diagnosis. However, we lack, at present, a clinical practice guideline on diagnostic approach in 46, XY DSD from this part of the globe. Moreover, debate persists regarding the timing and cut-offs of different hormonal tests, performed in these cases. The consensus committee consisting of 34 highly experienced endocrinologists with interest and experience in managing DSD discussed and drafted a consensus statement on the diagnostic approach to 46, XY DSD focussing on relevant history, clinical examination, biochemical evaluation, imaging and genetic analysis. CONTENT: The consensus was guided by systematic reviews of existing literature followed by discussion. An initial draft was prepared and distributed among the members. The members provided their scientific inputs, and all the relevant suggestions were incorporated. The final draft was approved by the committee members. SUMMARY: The diagnostic approach in 46, XY DSD should be multidisciplinary although coordinated by an experienced endocrinologist. We recommend formal Karyotyping, even if Y chromosome material has been detected by other methods. Meticulous history taking and thorough head-to-toe examination should initially be performed with focus on external genitalia, including location of gonads. Decision regarding hormonal and other biochemical investigations should be made according to the age and interpreted according to age-appropriate norms Although LC-MS/MS is the preferred mode of steroid hormone measurements, immunoassays, which are widely available and less expensive, are acceptable alternatives. All patients with 46, XY DSD should undergo abdominopelvic ultrasonography by a trained radiologist. MRI of the abdomen and/or laparoscopy may be used to demonstrate the Mullerian structure and/or to localize the gonads. Genetic studies, which include copy number variation (CNV) or molecular testing of a candidate gene or next generation sequencing then should be ordered in a stepwise manner depending on the clinical, biochemical, hormonal, and radiological findings. OUTLOOK: The members of the committee believe that patients with 46, XY DSD need to be approached systematically. The proposed diagnostic algorithm, provided in the consensus statement, is cost effective and when supplemented with appropriate genetic studies, may help to reach an aetiological diagnosis in majority of such cases.