Aims COVID-19 pandemic has massively impacted human health. We studied the effect of COVID-19 on outcome of Diabetic foot ulcers (DFUs). Objectives and Methods We recruited 483 people with DFUs from June 2020 to April 2022 (pandemic) together with a matched group of 226 people with DFU from March 2019 to March 2020 (pre-pandemic). Primary endpoint was outcome of ulcers-healed or amputation (major/minor). It was sub-analysed into 3 waves of COVID-19. Secondary endpoint was healing of individual types of DFUs. Basic anthropometric data included site and type of ulcer (ischemic or neuropathic), duration, presence or absence of infection and Wagner's grading of DFUs was collected for all patients. Diagnosis of peripheral neuropathy was done by monofilament testing and peripheral arterial disease by handheld Doppler and ankle brachial index (ABI). Standardized treatment protocol was provided. All patients were monitored for 6 months. Results In the pandemic group 323 (66.9%) patients in whom ulcers healed, 70 (14.5%) underwent minor amputation, 11 (2.2%) major amputation, 29 (6%) were lost to follow up, 22 (4.6%) were not healed. Rate of healing of DFU was higher (66.9% vs 53.5%) and rate of amputation was lower (16.7% vs 23.4%) in the pandemic group than in the pre-pandemic group (P = 0.001 and 0.037 respectively). Rate of healing in first, second and third wave was 65.4%, 75.2%, 58.3% respectively (P = 0.001). Neuropathic ulcers though less prevalent (49.8% vs 57.8%) in the first two waves than in the third wave, healing was better (79.3% vs 75.6%) in the first two waves than in the third wave (P = 0.085 and 0.488 respectively). Similarly, amputation rates in ischemic and neuro-ischemic ulcers were greater in the third wave than first two waves (46.7% vs 15.7%, P = 0.049). Conclusion During the COVID-19 pandemic, healing of neuropathic ulcers was better, especially in the first and second waves and travel restriction may have accounted for this. However, worsening of ischemic and neuro-ischemic ulcers was observed with more amputation in these two groups. Conversely, in the third wave withdrawal of lockdown led to worsening of DFUs resulting in less healing and more amputation.

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.

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 3e5 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. & COPY; 2023 Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC). Published by Elsevier Ltd. All rights reserved.

Sulfonylureas (SU) continue to be a vital therapeutic category of oral hypoglycemic agents (OHAs) for the management of type 2 diabetes mellitus (T2DM). Physicians consider modern SU (gliclazide and glimepiride) as “safe and smart” choices for T2DM management. The presence of multiple international guidelines and scarcity of a national guideline may contribute to the challenges faced by few physicians in choosing the right therapeutic strategy. The role of SU in diabetes management is explicit, and the present consensus aims to emphasize the benefits and reposition SU in India. This pragmatic, practical approach aims to define expert recommendations for the physicians to improve caregivers’ knowledge of the management of T2DM, leading to superior patient outcomes.

Neuroendocrine tumors of the pancreas (PanNET) are rare and data on their epidemiology are limited. It is estimated that they possibly account for <3% of all pancreatic tumors, and approximately 4–8% of all neuroendocrine tumors. There has been a steady rise in the incidence of PanNET over the past few decades. The PanNET have a highly variable clinical presentation, malignant potential, and prognosis. They can be functional (associated with a hormone-secreted clinical syndrome) or nonfunctional. Less than 10% of PanNET are associated with inherited disorders, including multiple endocrine neoplasia, von Hippel–Lindau syndrome, neurofibromatosis type 1, and tuberous sclerosis complex. The classification of these rare tumors has evolved gradually since the early 1960s, and over time have become relatively complex. In order to overcome this limitation, the European Neuroendocrine Tumor Society (ENETS) proposed a tumor–node–metastasis (TNM) staging system in 2006 that also included a grading system. Subsequently, the World Health Organization (WHO) introduced a classification system in 2010 that endorsed and included the proliferation-based grading system proposed by the ENETS together with the classical histological based classification. The WHO recognized the need for a separate staging system and, together with the American Joint Cancer Committee (AJCC), adopted the TNM staging system proposed in 2009 by the International Union for Cancer Control (UICC/AJCC/WHO 2010 TNM). The PanNET were thus classified based on the WHO 2010 classification system into neuroendocrine tumors (grade 1 or grade 2) or neuroendocrine carcinomas (grade 3) according to their proliferative rate substantiated by the Ki-67 labeling index. They should also be staged, using one of the two existing TNM staging systems. Further modifications in the classification system can be expected because the current grading system does not clearly distinguish between grade 2 at the extreme edge of the range and low proliferative grade 3 carcinomas; moreover, the existence of two parallel TNM staging systems that describe slightly different extents of disease while using the same TNM terminology is confusing.

Discovered a hundred years ago, glucagon continues to amaze clinicians globally with its range of functions affecting the entire human physiology. Although initially it was considered just an opposer of insulin action, recent years have seen that glucagon has a plethora of effects on body metabolism. However, many aspects of the complex regulatory mechanisms of glucagon secretion and its impact on nutrient metabolism are yet to be clearly elucidated. Understanding the physiology of glucagon secretion and action is the key to the development of pharmacological agents which would impact on metabolic disorders. Glucagon secretion is regulated by a variety of factors, including meal type, paracrine hormone secretion from α and β cross-talk, incretin hormones, and the autonomic nervous system, among others. On the other hand, glucagon has manifold effects on glucose, fatty acid, and amino acid metabolism, as well as a significant impact on thermogenesis, satiety, and the cardiovascular system. This article collates the physiological mechanisms of glucagon secretion and action, incorporating the latest in glucagon research.

Objective There are no controlled studies on the role of systemic corticosteroids (CS) in patients with coronavirus disease 2019 (COVID-19). In the absence of high-quality evidence, understandably the recommendations from various organizations are cautious. Several randomized controlled trials are underway but shall take time to conclude. We therefore undertook a meta-analysis to ascertain the role of CS in the management of critically ill patients with COVID-19. Data Sources Electronic databases, including Pubmed, Cochrane library and Embase, were searched, using the keywords of interest and the PICO search technique, from inception to 12th April 2020. Study Selection Studies highlighting the use of CS in coronavirus infection with severe acute respiratory syndrome (SARS), Middle East Respiratory Syndrome (MERS) and COVID-19 were selected based on pre-determined inclusion criteria. Data extraction Data was extracted into an excel sheet and transferred to comprehensive meta-analysis software version 3, Biostat Inc., Englewood, NJ, USA, for analysis. Data synthesis Five studies with SARS-CoV-2 infection were included in the meta-analysis. The rate ratio (RR) for mortality in patients with SARS-CoV-2 infection was 1.26 (95% CI: 0.96-1.65, I 2 : 74.46), indicating lack of benefit of CS therapy on mortality in critically ill patients with COVID-19. The RR for mortality on analysis of the three studies that particularly reported on patients with significant pulmonary compromise secondary to SARS-CoV-2 infection was neutral (RR: 0.91, 95% CI: 0.63-1.33, I 2 : 63.38). Conclusions The use of CS in critically ill patients with COVID-19 did not improve or worsen mortality. Pending further information from controlled studies, CS can be used in critically ill patients with COVID-19 with ‘critical illness related corticosteroid insufficiency’ and moderate to severe ARDS without the risk of increased mortality.

This post-authorization study was conducted to evaluate the safety of insulin degludec/insulin aspart (IDegAsp) in adult patients with diabetes mellitus (DM) during routine clinical care under a real-world setting in India. Eligible patients received IDegAsp for a minimum of 12 months during routine clinical management. Data were collected at 0, 3, 6, and 12 months. In total, 1029 adult patients with DM were included; 65.2% (n = 671) were men; mean age was 55.0 ± 12.2 years, and the mean duration of diabetes mellitus was 10.8 ± 7.4 years. Thirty adverse events were reported in 23 patients (2.2%) during the follow-up: two adverse events in two patients were serious with fatal outcomes, which were unrelated to IDegAsp use. At baseline, there were 176 confirmed hypoglycemic events in 67 (6.7%) patients while they were on their previous treatment options. At 12 months of treatment with IDegAsp, 11 confirmed hypoglycemic events were reported in 11 (1.1%) patients since the previous visit; there were no reported episodes of severe hypoglycemia. Mean glycosylated hemoglobin value reduced from 9.5% ± 1.8% at baseline to 7.7% ± 1.1% at 12 months. This study showed the safety of IDegAsp in patients with diabetes mellitus over a period of 1 year during routine clinical care.

The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide, and its complications are highly contributing to mortality. Compared to oral hypoglycemic agents, reduction in HbA1c is maximum with insulin therapy. Evidence suggests the potential benefits of achieving normoglycemia with early intensive insulin therapy. Despite the high levels of uncontrolled T2DM in Indian patients, the use of insulin remains suboptimal. Initiation of insulin therapy in patients with T2DM is often inappropriately delayed due to physician's barriers. These include physicians’ inadequacy of skill and time required for insulin therapy, perceived complications of insulin therapy and perceived lack of treatment benefit. These barriers can be overcome by physician education and training, using effective patient education methods and tools, and bridging gaps to improve adherence by the patients. Pharmaceutical industry, government health authorities, medical institutions, healthcare professionals and patients can help to overcome the clinical inertia for the initiation and titration of insulin in patients with type 2 diabetes.

Background and aims: Insulin therapy is an integral part of diabetes management. However, reliable and easily accessible information on a number of basic facts concerning insulin therapy, including storage of insulin, managing insulin therapy during travel, nuances of insulin use while driving, and dose adjustments during sick days is lacking. This document aims to make readily available, reliable, and easy to implement information on these essential but relatively less discussed aspects of insulin therapy. Method: Literature search was performed using PubMed and Cochrane Library from inception till 1st of July 2019. The relevant topics were reviewed by a panel of 5 specialists and 23 contributing physicians and endocrinologists, who had assembled at Bengaluru, India for the 13th National Insulin Summit. After a thorough review of the literature, and following detailed discussions, the committee arrived at these recommendations. Results: Unopened vials and cartridges of insulin should be stored at 2 degrees C-8 degrees C in a refrigerator and protected from direct sunlight. For opened vials and in-use cartridges, manufacturer's instructions must be followed at all times. While traveling by air, dose adjustments are required only when flying across more than five time zones in the east or west directions. Insulin therapy should not be omitted or stopped during an acute illness; rather the doses need careful adjustments based on self-monitoring of blood glucose. Conclusion: Recommendations and guidelines, covering many common aspects of insulin therapy are readily available. This consensus document aims to make recommendations for those essential aspects of insulin therapy that are crucial for its success but are relatively less known and less discussed. (C) 2021 Published by Elsevier Ltd on behalf of Diabetes India.

ABSTR A C T Objectives: Depression is common in diabetes and has significant impact on health out-comes. Suicidal ideation also forms a part of the spectrum of diabetes and coexistent depression. To assess the predictors of depression as well as its prevalence in Type 2 Dia-betes Mellitus (T2DM) patients, we conducted a cross sectional study entitled "DEPression in DIABetes" (DEPDIAB). Material and methods: A cohort of consecutive 1371 T2DM patients from Eastern India suf-fering from diabetes greater than 1 year was assessed in a cross-sectional survey in 9 dif-ferent hospitals and medical polyclinics in Kolkata, India for depression by administering the 9-item PHQ - 9 and Beck depression scales. Socioeconomic status was assessed by the "Revised Kuppuswamy and B G Prasad socio-economic scales for 2016", a validated scoring system for assessing the socioeconomic status of Indian patients. Results: In our study 836 patients (60.9%) were male and 535 (39.02%) were female. 56 patients (4.1%) met the criteria for major depression and 494 patients (36.16%) for minor depression. No sign of depression was found in 816 patients (59.74%). Depression was strongly associated with younger age (18-40 years vs. >60 years) [OR-2.09; 95% CI 1.11- 3.96], female sex [OR-1.31; 95% CI 1.11-2.01], low socioeconomic status [OR-2.69; 95% CI 1.34-3.79], poor compliance [OR-5.05; 95% CI 2.79-8.13], hypoglycemia [OR 1.466; 95% CI 1.076-1.999] and difficulty in managing day-to-day activities [OR-4.648; 95% CI 3.450- 6.262] Suicidal ideation was detected in 201 patients (14.8%). Among patients who had repeated attacks of hypoglycemia (>1 episode per month), 22% experienced suicidal ideation. This was significantly higher than in patients who had not suffered from hypoglycemia (12%) (p < 0.0001). Patients with HbA1C of 7% or lower experienced statistically significantly lesser suicidal ideation than patients with a higher HbA1C (12% vs. 16.8% {p = 0.016}). Suicidal ideation did not correlate withbody mass index (BMI), fasting plasma glucose (FPG) or insulin usage. Conclusions: We found a high prevalence of depression in T2DM patients in Eastern India. Younger age, female sex, lower socio-economic status, poor compliance, hypoglycemia, and difficulty in managing day to day activities emerged as significant predictors of depression in this study. Recurrent episodes of hypoglycemia were an independent risk factor for suicidal ideation in patients with depression. Depression was not significantly associated with co morbidities associated with T2D and surprisingly insulin usage was not associated with increased depression. (c) 2021 Elsevier B.V. All rights reserved.

Background: Though testosterone replacement therapy in men with organic hypogonadism is established, its role in men with type 2 diabetes mellitus (T2DM) and functional hypogonadism is unclear. Methods: Thirteen experts addressed ten topic-specific questions after an in-depth review of literature, where all relevant issues were critically evaluated. Results: Ten recommendations concerning diagnosis and management of men with T2DM and functional hypogonadism have been put forward. Conclusion: Routine measurement of serum testosterone in all, and inappropriate replacement of testosterone in asymptomatic T2DM men with functional hypogonadism and borderline low serum testosterone values, is not recommended. (C) 2021 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Evidence suggests a major contribution of postprandial glucose (PPG) excursions to the increased risk of micro- and macro-vascular complications in individuals with type 2 diabetes mellitus (T2DM). Administration of bolus insulin remains a very effective therapeutic option for PPG control. The aim of this expert group recommendation document was to provide practical and easy-to-execute guidelines for physicians on the appropriate use of bolus insulin in the management of T2DM. A panel of key opinion leaders from India reviewed and discussed the available clinical evidence and guideline recommendations on the following topics: (1) optimum control of PPG; (2) choice of bolus insulin; and (3) special situations and practical considerations. The expert panel critically analyzed the current literature and clinical practice guidelines and factored their rich clinical experience to develop a set of nine expert group recommendations for the effective use of bolus insulin. These recommendations will not only result in a more evidence-based application of bolus insulin in the clinical setting but also trigger further research and provide a valuable base for the development of future guidelines on the use of bolus insulin in the management of individuals with T2DM.

Though testosterone replacement therapy in men with organic hypogonadism is established, its role in men with type 2 diabetes mellitus (T2DM) and functional hypogonadism is unclear.Thirteen experts addressed ten topic-specific questions after an in-depth review of literature, where all relevant issues were critically evaluated.Ten recommendations concerning diagnosis and management of men with T2DM and functional hypogonadism have been put forward.Routine measurement of serum testosterone in all, and inappropriate replacement of testosterone in asymptomatic T2DM men with functional hypogonadism and borderline low serum testosterone values, is not recommended.

Aims and Methods: Effect of angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) on outcomes in patients with coronavirus disease 2019 (COVID-19) is uncertain. Available evidence is limited to a few retrospective observational studies with small number of patients. We did a meta-analysis to assess the effect of ACEi/ARB in patients with COVID-19 on severity of disease, risk for hospitalisation, and death compared to those not on ACEi/ARB. We searched the Cochrane library, PubMed, Embase, ClinicalTrial.gov and medRxiv for studies published until 25.04.2020. Inclusion criteria included all studies with patients with confirmed COVID-19 either taking, or not taking, ACEi/ARB. Depending on degree of heterogeneity, fixed or random effect model was selected to calculate effect size (Odds ratio). Results: Six studies were eligible for this meta-analysis. These included 423 patients on ACEi/ARB, and 1419 not on ACEi/ARB. Compared to patients with COVID-19 not on ACEi/ARB, there was a statistically significant 43% reduction (OR 0.57, CI: 0.37-0.88, I2: 0.000) in the odds of death in those on ACEi/ARB. There was a statistically non-significant 38% reduction (OR: 0.62, 95% CI: 0.31-1.23, I2=70.36) in the odds of developing severe disease and 19% reduction (OR 0.81; 95% CI: 0.42-1.55, I2: 0.000) in the odds of hospitalisation among those on ACEi/ARB. Discussion: It is safe to use ACEi/ARB in patients with COVID-19 requiring these medications for associated comorbidities. Although limited by confounding factors typical of a meta-analysis of retrospective observational studies, our data suggests that use of these medications may reduce the odds of death. Conclusion: Our meta-analysis of the updated studies on SARS-CoV-2 reassures the medical fraternity on the use of and continuation of ACEi/ARB, supporting all recent recommendations .

BACKGROUND AND AIMS:People with type 2 diabetes mellitus (T2DM) have increased morbidity and mortality due to coronavirus disease-19(COVID-19). It has been speculated that use of pioglitazone might increase such risk. The aim of our brief commentary is to review the safety of pioglitazone in people with T2DM and mild/moderate COVID-19. METHODS:We searched PubMed database using specific keywords related to our aims till May 15, 2020. Full text of relevant articles published in English language were retrieved and reviewed. RESULTS:Medications, including pioglitazone, that upregulate tissue expression of angiotensin converting enzyme 2 (ACE2), might have a dual role in COVID-19; on the one hand they might increase risk of infection as SARS-CoV2 uses ACE2 as a coreceptor to enter alveolar cells, but on the other hand, by reducing angiotensin II levels, they can protect against acute lung injury. There is no evidence to date that pioglitazone upregulates ACE2 in the alveolar cells; rather, there is evidence from animal studies of upregulation of ACE2 in insulin sensitive tissues, which might have a protective effect on lung injury. Moreover by moderating the exaggerated host proinflammatory response, pioglitazone can potentially reduce SARS-CoV-2 driven hyperinflammation. CONCLUSIONS:Pioglitazone has more potential for benefit than harm, and can be continued in people with T2DM and mild/moderate COVID-19, unless there are specific contraindications for its use. There is an urgent need to assess clinically relevant outcomes in people with diabetes and COVID-19 based upon baseline antidiabetes therapy, in particular pioglitazone.

Background and aims: Morbidity and mortality from coronavirus disease 2019 (COVID-19) is higher among people with diabetes mellitus (DM), hypertension, and cardiovascular disease (CVD). Statins are used in the majority of people with DM and CVD. This mini-review discusses the current understanding of benefit-risk ratio of use of statins in COVID-19. Methods: We searched PubMed database using specific keywords related to our aims till June 12, 2020. Full text of relevant articles published in English language were retrieved and reviewed. Results: Statins, with their immunomodulatory, anti-inflammatory, anti-thrombotic, and anti-oxidant properties, have the potential to reduce severity of lung injury in, and mortality from, severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) infections. Statin-induced upregulation of angiotensinconverting enzyme-2 (ACE2) has the potential to reduce lung injury from excess angiotensin II. By disrupting lipid rafts, statins have the potential to reduce viral entry into cells. However, benefit-risk ratio of its complex interaction with MYD88 gene expression on outcomes in COVID-19, and the putative role of low serum LDL cholesterol in increasing severity of SARS-CoV2 infection need further clarification. Conclusions: People with COVID-19, who are already on statins for an underlying co-morbid condition, should continue on it unless there are specific contraindications. De-novo use of statins in people with COVID-19 with no underlying co-morbidity might be beneficial but awaits substantiation in clinical trials; till that time, de novo use of statins in COVID 19 should be limited to a clinical trial setting. (C) 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Type 2 Diabetes Mellitus (T2DM) is a well-recognized risk-factor for heart failure (HF). Among five modifiable risk factors studied for their influence on the population burden of HF in 14,709 persons in the Atherosclerosis Risk in Community study, namely smoking, elevated low-density lipoproteins, diabetes, hypertension, and obesity, diabetes was associated with the largest incidence rate differences; it was estimated that a 5% reduction in the prevalence of diabetes shall approximately prevent 30,000 incident HF cases in the US population. 1 Among the 5,209 men and women followed for 18 years in The Framingham Heart Study, prior diabetic status resulted in a 2-fold increase in risk of congestive HF (CHF) in men and 5-fold increase in risk in women compared to the nondiabetic cohort.2 A systematic review of observational studies published in 2013 suggested that each 1% rise in glycated hemoglobin (HbA1c) value led to a 15% increase in the risk of CHF.3

Personalized medicine is an individualized and stratified approach to the management of a disease. Personalized medicine can reform the prevention, prediction, and management of diabetes. Use of genetic information in polygenic and monogenic forms of diabetes can help to identify genetic variants and reclassify patients into pathophysiological subgroups. Targeted diagnostic, preventive, and therapeutic interventions can be defined for these groups for effective management of diabetes. Pharmacogenetics combines genotypic and phenotypic factors to develop personalized care in various pathophysiological subgroups of persons with diabetes. Personalized medicine finds wider utility in monogenic (especially Maturity Onset Diabetes of the Young (MODY) and Neonatal Diabetes Mellitus [NDM]) than in polygenic, diabetes. The most frequently mutated genes in MODY include HNF1A and HNF3A. the common genes responsible for NDM include KCNJ11 and ABCC8 (SUR) genes. These genes influence various aspects of glucose metabolism such as β-cell K-ATP channel modulation, production of insulin and development of pancreas. The Madras Diabetes Research Foundation has fostered research in personalized medicine for diabetes based upon genetic information and has developed a national registry for neonatal diabetes and other monogenic form of diabetes.

Introduction. This expert review aims to address the epidemiology and pathophysiology of cardiovascular disease (CVD) in persons with type 2 diabetes mellitus (T2DM), help understand the various statistical considerations and interpretational nuances of cardiovascular outcome trials (CVOTs) in general, and discuss in particular, the CVOTs with insulins, and their impact on the choice of insulins in day-to-day clinical practice. Material and methods. The expert panel critically analysed published data from observational studies, randomized clinical trials, meta-analyses and CVOTs regarding cardiovascular (CV) safety of insulin preparations, and agreed on a series of consensus statements supported by available scientific evidence and the collective clinical judgement of the experts. Results. A proportion of persons with T2DM have a high risk of CVD and CV mortality, which is partly contributed by insulin resistance-related, and hyperglycaemia-related, risk factors. Over the past decade, CVOTs have become an integral part of the drug approval process of anti-diabetic therapies by the United States Food and Drug Administration (FDA). Most insulin preparations in use today, barring a few modern insulins, were introduced much before this regulatory requirement was put in place, and hence, have not undergone rigorous CVOTs. There is a large body of observational data concerning the CV safety of insulin preparations, which are often confusing and, at times, contradictory. In this background, it is reassuring to note that CVOTs of two basal insulin analogues, namely insulin glargine, studied in the Basal Insulin and Cardiovascular and Other Outcomes in Dysglycaemia Trial (ORIGIN), and insulin degludec, studied in the Efficacy and Safety of Degludec versus Glargine in Type 2 Diabetes Trial (DEVOTE), established their long-term CV safety. The DEVOTE trial provided additional safety data reporting fewer severe hypoglycaemic events with insulin degludec in comparison to insulin glargine. Conclusions. This review critically analyses the two CVOTs of basal insulin analogues, in tandem with a general review of the methodological and interpretational aspects of CVOTs in general. The long-term CV safety of analogue basal insulins is discussed. The lack of CVOTs with prandial and pre-mixed insulins, either human or analogue, was identified as the main research gap in this area.