Effect of a multicomponent quality improvement strategy on sustained achievement of diabetes care goals and macrovascular and microvascular complications in South Asia at 6.5 years follow-up: Post hoc analyses of the CARRS randomized clinical trial.

BACKGROUND: Diabetes control is poor globally and leads to burdensome microvascular and macrovascular complications. We aimed to assess post hoc between-group differences in sustained risk factor control and macrovascular and microvascular endpoints at 6.5 years in the Center for cArdiovascular Risk Reduction in South Asia (CARRS) randomized trial. METHODS AND FINDINGS: This parallel group individual randomized clinical trial was performed at 10 outpatient diabetes clinics in India and Pakistan from January 2011 through September 2019. A total of 1,146 patients with poorly controlled type 2 diabetes (HbA1c ≥8% and systolic BP ≥140 mm Hg and/or LDL-cholesterol ≥130 mg/dL) were randomized to a multicomponent quality improvement (QI) strategy (trained nonphysician care coordinator to facilitate care for patients and clinical decision support system for physicians) or usual care. At 2.5 years, compared to usual care, those receiving the QI strategy were significantly more likely to achieve multiple risk factor control. Six clinics continued, while 4 clinics discontinued implementing the QI strategy for an additional 4-year follow-up (overall median 6.5 years follow-up). In this post hoc analysis, using intention-to-treat, we examined between-group differences in multiple risk factor control (HbA1c <7% plus BP <130/80 mm Hg and/or LDL-cholesterol <100 mg/dL) and first macrovascular endpoints (nonfatal myocardial infarction, nonfatal stroke, death, revascularization [angioplasty or coronary artery bypass graft]), which were co-primary outcomes. We also examined secondary outcomes, namely, single risk factor control, first microvascular endpoints (retinopathy, nephropathy, neuropathy), and composite first macrovascular plus microvascular events (which also included amputation and all-cause mortality) by treatment group and whether QI strategy implementation was continued over 6.5 years. At 6.5 years, assessment data were available for 854 participants (74.5%; n = 417 [intervention]; n = 437 [usual care]). In terms of sociodemographic and clinical characteristics, participants in the intervention and usual care groups were similar and participants at sites that continued were no different to participants at sites that discontinued intervention implementation. Patients in the intervention arm were more likely to exhibit sustained multiple risk factor control than usual care (relative risk: 1.77; 95% confidence interval [CI], 1.45, 2.16), p < 0.001. Cumulatively, there were 233 (40.5%) first microvascular and macrovascular events in intervention and 274 (48.0%) in usual care patients (absolute risk reduction: 7.5% [95% CI: -13.2, -1.7], p = 0.01; hazard ratio [HR] = 0.72 [95% CI: 0.61, 0.86]), p < 0.001. Patients in the intervention arm experienced lower incidence of first microvascular endpoints (HR = 0.68 [95% CI: 0.56, 0.83), p < 0.001, but there was no evidence of between-group differences in first macrovascular events. Beneficial effects on microvascular and composite vascular outcomes were observed in sites that continued, but not sites that discontinued the intervention. CONCLUSIONS: In urban South Asian clinics, a multicomponent QI strategy led to sustained multiple risk factor control and between-group differences in microvascular, but not macrovascular, endpoints. Between-group reductions in vascular outcomes at 6.5 years were observed only at sites that continued the QI intervention, suggesting that practice change needs to be maintained for better population health of people with diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01212328.

Management of Hypertension in Patients with Type 2 Diabetes Mellitus: Indian Guideline 2024 by Association of Physicians of India and Indian College of Physicians.

In India and the Southeast Asian population, hypertension and type 2 diabetes mellitus (T2DM) are the leading lifestyle-related diseases, responsible for a majority burden of morbidity and mortality. Multiple population-spanning studies have revealed the staggering prevalence of both diseases in India, and the prevalence of both will only increase further due to factors such as an aging population, rapid urbanization, increased obesity, and sedentary lifestyles. More than 50 percent of hypertensive patients in India are also diagnosed with T2DM, and a detailed management protocol for the same is required, especially when a major portion of the disease is managed at the primary care level. The Association of Physicians of India (API) guidelines for the management of hypertension in patients with T2DM have been formulated based on consultation with leading physicians, cardiologists, diabetologists, and endocrinologists of India and Southeast Asia, keeping in mind the challenges faced by the patients in these countries and the appropriate management protocols that will be beneficial. While standard office-based blood pressure (BP) measurement forms the cornerstone of hypertension diagnosis and demands a uniform methodology to be followed, home blood pressure monitoring (HBPM) is recommended for long-term follow-up with validated devices. Ambulatory blood pressure monitoring (ABPM) offers comprehensive insights crucial for cardiovascular (CV) risk stratification. The complications of diabetic hypertension can span from increased CV risk, heart failure (HF), and renal dysfunction, and nonpharmacological and pharmacological management should be aimed toward not only control of the BP values but also protecting the end organs. While nonpharmacological measures include a focus on nutrition and diet, they also focus on approaches to weight loss, including a novel section covering the benefits of yoga. The guideline also focuses on a novel section of factors influencing CV risk, especially in the Indian population. For the pharmacological management, the guidelines address each of the categories of antihypertensive drugs, emphasizing the significance of combination therapies in the management of diabetic hypertension. In line with leading global guidelines for the management of hypertension in T2DM, for diabetic patients who often struggle with BP management and carry a high CV risk, the recommended dual combination antihypertensive therapy is particularly crucial and should be considered as first-line management therapy. While angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) play a highly beneficial role in the management of diabetic hypertension, a combination of ACEi or ARB with dihydropyridine calcium channel blockers (DHP-CCBs) is recommended to reduce the risk of complications and enhance patient adherence. To achieve the target of effective BP control and end-organ protection, it is beneficial and recommended to include newer CCBs (e.g., cilnidipine) in the management protocol in combination with ACEi/ARBs. Combination therapy including ARBs and DHP-CCBs should be preferred over ß-blockers and thiazides. Among the CCBs, cilnidipine, a novel molecule, is a more effective and safer option for diabetic hypertensive patients in India. ß-blockers should be used if there is a history of myocardial infarction (MI), HF, coronary artery disease (CAD), or stable angina along with the initial hypertensive regimen. The guideline also focuses on the novel reno- and cardioprotective molecules such as finerenone and sodium-glucose cotransporter 2 inhibitors (SGLT2i) and their benefits in the management of diabetic hypertension.

Responsible Use of Oral Corticosteroids in People with Comorbid Diabetes: An Expert Consensus.

Globally, diabetes mellitus (DM) is a substantial contributor to morbidity and mortality. Comorbidities and intercurrent illnesses in people with diabetes may necessitate the use of steroids. Acute as well as chronic use of steroids contributes substantially to the development of various complications. Despite this, there are no standard guidelines or consensus to provide a unified approach for the rational use of steroids in people with diabetes. Also, there is scant harmonization among clinicians with the use of different steroids in routine practice. To address the inconsistencies in this clinical arena, the consensus working group (CWG) formulated a unified consensus for steroid use in people with diabetes. In people with diabetes, the use of steroids causes hyperglycemia and may precipitate diabetic ketoacidosis (DKA). An increase in weight is directly related to the dose and duration of the steroid therapy. Steroid-related alterations in hyperglycemia, dyslipidemia, and hypertension (HTN) add to the increased risk of cardiovascular (CV) disease. The risk of complications such as infections, osteoporosis, myopathy, acne, cataracts, and glaucoma may increase with the use of steroids. Appropriate and timely monitoring of these complications is necessary for early detection and treatment of such complications. Given the systemic effects of various antihyperglycemic drugs, there is a possibility of aggravating or diminishing the specific complications. Preference to a safer steroid is required matching the steroid dose equivalence and individualizing patient management. In conclusion, short-, intermediate-, or long-term use of steroids in people with diabetes demands their rational use and holistic approach to identify, monitor, and treat the complications induced or aggravated by the steroids.

Public Health System's Preparedness to Address Polycystic Ovarian Syndrome: A Rapid Assessment Survey of Health-care Providers in India.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders largely affecting women of reproductive age group. OBJECTIVES: This study aimed to understand the Indian public health-care systems' preparedness in addressing PCOS. MATERIALS AND METHODS: A multicentric rapid assessment cross-sectional study was undertaken among 173 health-care providers serving across various public health-care facilities in India. This study was a component of a larger task force study that aimed to estimate the community-based prevalence of PCOS in India. Information on PCOS cases reported that knowledge about PCOS diagnosis, management practices, availability of diagnostic facilities, and drugs was explored. RESULTS: Irregular menstrual cycle was the most commonly reported PCOS symptom. Most of the health-care providers (HCPs) lacked correct knowledge about diagnostic criteria and investigation needed for the diagnosis of PCOS. Diagnostic facilities and drugs were inadequate. However, some facilities had access to investigations through public-private partnerships. Awareness programs on PCOS in the community were negligible, and PCOS cases were not documented. Training HCPs on PCOS along with the availability of specialists and strengthening diagnostic facilities were some major demands from the HCPs. CONCLUSION: Results suggest the need for training HCPs, strengthening infrastructure with good referral linkages, and adequate supply of drugs to help improve PCOS management at public health-care facilities in India. There is a need to develop national technical and operational guidelines to address PCOS using a multidisciplinary approach across all levels of care. Creating demand for services and advocating healthy lifestyles through community awareness can help early diagnosis and prevention of complications.

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

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

Assessment of Biomedical Waste Generation in Dialysis Units: A Prospective Observational Study-Is it Time for "Green Dialysis"?

Introduction: Chronic kidney disease and as a consequence end-stage kidney disease (EKSD) is increasing globally. More and more people across the world are requiring hemodialysis (HD). The HD procedure produces a large quantity of biomedical waste. In addition, HD consumes a large quantity of water. In this study, we estimated the waste generated from our government-funded HD unit. Materials and methods: It is a prospective study that was carried out in the dialysis unit in the nephrology department over a period of 1 year. The daily dialysis waste generated by the unit was measured using a spring balance. The proportion of plastic and nonplastic waste was determined. The quantity of biomedical waste generated per person in 1 year was calculated. Water input to the dialysis unit was noted. Water consumption per dialysis was calculated. Liquid chemical waste consumed was determined. Electricity consumed by the unit was measured by the electricity meter. The cost of waste disposal was calculated. The cost of electricity consumption and water consumption was also calculated. Results: The approximate weight of waste disposables generated in one dialysis was 0.75 kg. Approximately each person generates 1.29 kg of waste per dialysis. Each dialysis required 125 L of reverse osmosis (RO) water and to generate 125 L of RO water 250 L of raw water was used. This happens as 125 L of water are rejected during the generation of 125 L of RO water. Thus, the net water consumption for each dialysis was 250 L. Chemical waste generated per dialysis includes 90 mL citric acid per dialysis and 130 mL bleach. Each dialysis consumes 3 kWh (three units) of electricity. The cost of electricity for each dialysis was 25.5 INR and the cost of water was 25 INR per dialysis. The cost of waste disposal for each dialysis bed was 6 INR. Discussion: Each dialysis patient produced 1.29 kg of waste per dialysis which was like other studies. Unlike other studies, the waste was not being reprocessed or recycled. Conclusion: Hemodialysis produces substantial biomedical waste. Proper waste disposal techniques and policies to promote reduction, reuse, and recycling will go a long way toward promoting green dialysis and reducing environmental as well as economic burdens. How to cite this article: Sahay M, Sahay RK, Seshadri B, et al. Assessment of Biomedical Waste Generation in Dialysis Units: A Prospective Observational Study-Is it Time for "Green Dialysis"? J Assoc Physicians India 2023;71(10):49-52.

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.

Diabetes Care And Transgender Health: Clinical Pearls.

Diabetes and other cardiometabolic diseases occur across the world, and do not discriminate between populations. This communication reviews the epidemiology and etiology of diabetes in the transgender population, and highlights clinical issues that must be kept in mind while evaluating and managing the condition. It adds value to existing literature by equipping health care professionals with specific skills designed to enhance diabetes care delivery, and results, in transgender individuals.

The 5A model for non- communicable disease advocacy.

We share a comprehensive 5A model which puts in perspective a clear-cut method to approach and address non communicable disease (NCD) advocacy. We suggest that the first step towards NCD control is awareness amongst health care professionals, and acceptance of their responsibility towards public health. Once this is done, active assertion follows, and leads to action on the ground. Regular audit, however, is necessary, to ensure effective and efficient advocacy for NCD. This model should be followed in all health care settings, including primary care diabetes.

Management of Hypertension in Patients with Diabetes: A Comprehensive Review of the Perceptions and Practices of Health Care Providers in India.

OBJECTIVES: This study evaluated the perception and practices of health care providers (physicians, diabetologists, and endocrinologists) regarding the treatment of hypertension in patients with diabetes in India. METHODS: Health care providers throughout India who treated patients with diabetes and hypertension were invited to participate in an online survey and periodic 21 virtual meetings. They were questioned about their perception and practices in managing these patients, and strategies to improve blood pressure (BP). RESULTS: The online survey was completed by 2,513 health care providers, and 344 participated in virtual meetings. More than 50% reported that 31-50% of their patients with diabetes also had hypertension. Home BP monitoring was recommended by 88%, and lifestyle modifications were consistently recommended. Choice of antihypertensive treatment varied based on comorbidities, and a renin-angiotensin system blocker plus a calcium channel blocker (CCB) was the most common combination for dual antihypertensive therapy. Suggested strategies to improve BP control included patient awareness/education, lifestyle modifications, better follow-up/monitoring, and optimization of therapy. CONCLUSION: Indian health care providers were aware of clinical recommendations and practices regarding treatment of patients with diabetes and hypertension, and generally make clinical decisions consistent with current guidelines. Optimization of care for these patients is essential to reduce cardiovascular disease risk and improve patient outcomes.

An Expert Group Consensus Statement on "Approach and Management of Prediabetes in India".

The prevalence of prediabetes, a forerunner of diabetes is very high, and its conversion to diabetes is also more rapid among Asian Indians. Prediabetes also predisposes to the development of macrovascular and to a lesser extent of microvascular complications of diabetes. In a large community-based epidemiological study, the Indian Council of Medical Research-India Diabetes (ICMR-INDIAB), data reported an overall prevalence of prediabetes of 10.3%, derived from 15 Indian states. This shows that the diabetes epidemic is far from over as many of them may soon convert to diabetes. Prediabetes, however, should not be considered a path to diabetes rather it should be a window of opportunity for the prevention of diabetes. This early screening, detection, and treatment of prediabetes should be made a national priority. Several countries have introduced lifestyle programs to prevent diabetes and, when indicated, pharmacological intervention with metformin as well. This consensus statement outlines the approaches to screening and lifestyle and pharmacological management of prediabetes in Asian Indians.

Prediabetes: A pragmatic triage for preventive pharmacotherapy.

Prediabetes is a commonly encountered condition that bears a significant risk of progression to diabetes. While lifestyle modification remains the treatment of choice, drug therapy is emerging as a therapeutic option to prevent its progression to diabetes and associated complications. This paper proposes a comprehensive triage system to identify persons with prediabetes who may benefit from preventive pharmacotherapy.

A hundred years on: The role of human insulin.

There are multiple insulin preparations, and strengths, available in various delivery devices. Modern insulin analogues are characterised by better safety and tolerability, and are increasingly being used across much of the world. Does there still exist a role for human insulin? This brief communication explores the potential indications for human insulin, while discussing the concerns and caveats related to its use, and suggesting ways of safe and smart use of human insulin.

Thyroid tantrums in teenagers.

Thyroid disorders can be difficult to manage, especially in childhood and adolescence. Sudden fluctuations may occur in thyroid function, due to a variety of physiological, pathological, pharmacological and psychosocial reasons. This communication describes the etiology and management of such conditions. We term these fluctuations as thyroid tantrums, and define them as sudden disruptions in thyroid function, in persons on treatment for hypothyroidism. Thyroid tantrums may be recognized clinically or on the basis of laboratory findings. A pragmatic approach to management, focusing on therapy assessment, testing technique, targeting biomedical illness and training, is suggested in this article.

A Prospective Validation Survey to Assess Usage of Premix Insulins in Management of Diabetes with Respect to the Recommendations Enlisted in Indian Guidelines.

OBJECTIVE: Widely used in the management of diabetes, the premix insulin therapy is influenced by several patient preferences and physician choices. The present survey aims to provide specific recommendations based on published data for appropriate management of T2DM with premix insulins. METHODS: We administered an online questionnaire where the respondent physicians were requested to go-through the published India specific and international guidelines before the survey. The respondents were requested to answer the electronic survey based on their clinical experiences with patients having diabetes. RESULTS: Overall, 1408 doctors participated in the survey. Majority of physicians preferred a premix insulin regimen for initiation. Short-term therapy with premix insulins in insulin-naive T2DM patients with symptomatic hyperglycemia and/ or glucotoxicity was strongly recommended by 40.7% physicians. Initiation of insulin early in the course of T2DM was recommended by 58.7% of physicians in cases where glycemic goals were not achieved by non-insulin drugs. Premix insulin analogues were preferred over human premix insulins by more than half of participating physicians (52.2%). Premix insulin analogues were preferred over basal insulins by 49.8% of physicians. Nearly half (44.5%) of the physicians recommended initiation of twice daily premix analogues over once daily basal insulins to achieve recommended glycemic targets. Around forty two percent (41.9%) physicians strongly believed that twice daily/thrice daily premix insulin analogues provide comparable glycemic control and safety to basal plus regimen with additional benefit of simplicity. During Ramadan premix insulin analogues were recommended over human premix by 46.5% physicians in view of improved safety and flexibility of dosing. SUMMARY: Majority of Indian physicians concur with the recommendations of INCG 2017 guidelines. Premix insulins were preferred for insulin initiation. IDegAsp was preferred over other premix insulins by majority of physicians. Twice daily premix insulins were recommended for intensification.

The andro-accelerator hypothesis.

Testosterone levels are known to decline with advancing age. However, there are frequent reports of inappropriate social behaviour involving middle-aged men, suggestive of hyperandrogenic state. The andro-accelerator hypothesis seeks to explain this phenomenon. This states that external stimuli, both asexual and sexual in nature, can increase or accelerate testosterone production, by stimulating the hypothalamo-pituitary-testicular axis, and resetting this axis at a higher level. This article discusses the concepts of andro-conditioning due to endocrine disruptor stimuli or endocrine disruptor social content, explores the clinical and public health relevance of the andro-accelerator hypothesis, and calls for a focus on addressing androgen imbalance, achieving "androequanimity", rather than treating andropause as a disease.

Oncocrinology.

Oncocrinology is the science which studies the complex bi-directional relationship between cancer and the endocrine system, including pathophysiological links, clinical presentation and the impact of cancer treatment and endocrine therapy. This review describes the vast spectrum of the complex, multifacted relationship between the endocrine system and malignancy. It also includes the endocrine aspects of anti-cancer treatment, and the need for oncovigilance with endocrine therapy.

The SECURE model: A comprehensive approach for obesity management.

With rapidly increasing prevalence of obesity worldwide, it has become imperative to generate a comprehensive and easy to use clinical model for its management. We propose a simplified yet systematic approach to an obese patient, for a personalised patient centric obesity management. The SECURE model encompasses three domains in evaluation of the patient (Severity assessment, Etiological evaluation and Comorbidity workup) and the other three pillars for obesity treatment (Urge life style changes, Role of medications and surgery and Expected goal setting). This provides a clinical action checklist that may be useful even in other chronic non communicable disorders.

The glycaemic personality: A SURE framework of person-centred choice in diabetes care.

Diabetology is becoming more and more complex, and requires simple yet comprehensive models to facilitate appropriate management of the syndrome. This communication highlights the concept of glycaemic personality, defined as the sum of all attributes, both biomedical and psychosocial, which influence the glucophenotype of an individual. This concept can be explained by using the SURE model, which lists four factors that influence choice of glucose-lowering therapies and their targets. These include the Severity and Style of hyperglycaemia, Urgency and Utility of glucose control, Relative Risk of hypoglycaemia, and Expected adherence to therapy and Expectations of the person living with diabetes.

Superior efficacy of insulin degludec/liraglutide versus insulin glargine U100 as add-on to sodium-glucose co-transporter-2 inhibitor therapy: A randomized clinical trial in people with uncontrolled type 2 diabetes.

AIM: To investigate the efficacy and safety of insulin degludec/liraglutide (IDegLira) versus insulin glargine 100 units/mL (IGlar U100) as add-on to sodium-glucose co-transporter-2 (SGLT2) inhibitor therapy. MATERIALS AND METHODS: In this 26-week, phase IIIb, open-label, parallel-group, treat-to-target trial, conducted at 74 sites in 11 countries, insulin-naïve people aged ≥18 years with glycated haemoglobin (HbA1c) 53-97 mmol/mol (7.0-11.0%), body mass index 20-40 kg/m2 and inadequately controlled type 2 diabetes (T2D) on SGLT2 inhibitor ± oral antidiabetic drugs were randomized 1:1 to once-daily IDegLira or IGlar U100, both as add-on to existing therapy. The primary endpoint was change in HbA1c from baseline to week 26. RESULTS: A total of 210 participants were randomized to each treatment arm. Mean HbA1c reductions were 21 mmol/mol (1.9%-points) with IDegLira and 18 mmol/mol (1.7%-points) with IGlar U100; confirming non-inferiority (P < 0.0001) and superiority of IDegLira (difference in HbA1c change -3.90 mmol/mol; 95% confidence interval [CI] -5.45; -2.35 (-0.36%-points; 95% CI -0.50, -0.21)). Superiority for IDegLira over IGlar U100 was also confirmed for: body weight (difference -1.92 kg; 95% CI -2.64, -1.19); severe or blood-glucose-confirmed symptomatic hypoglycaemia (rate ratio 0.42; 95% CI 0.23, 0.75); total daily insulin dose (difference -15.37 U; 95% CI -19.60, -11.13). The overall treatment-emergent adverse event rate was higher with IDegLira as a result of higher increased lipase and nausea rates. CONCLUSIONS: The favourable safety and efficacy profile of IDegLira in people with uncontrolled T2D on SGLT2 inhibitors, and lower weight gain and hypoglycaemia risk versus IGlar U100, suggest that clinicians should consider IDegLira initiation in this population.