CME INDIA Presentation by Admin.

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Part – [1]

• Diabetes India 2022 is a platform, where clinicians, diabetes care providers, researchers and industries convene with the aim to promote, support and enhance the development of treatments for diabetes.
• The Diabetes India 2022 brings you the food for thought and stimulation for your grey cells.
• Here we present the best takeaways from the 12th World Congress of Diabetes India – Diabetes India 2022

Diabetes Care: Time to Concentrate on Comprehensive Care

Dr. S. R. Aravind Bengaluru (Presidential Oration)

• Diabetes mellitus is one of the most serious chronic illnesses in the world due to its prevalence, economic and social effects, and negative impact on the quality of life of the affected people.
• The diagnosis implies changes in life habits especially related to feeding, physical activity and constant self-care, requiring greater personal autonomy.
• Complications – both microvascular and macrovascular can lead to poor quality of life. Physically, mentally and economically draining leading to both patient and family suffering.
• Mysteries of diabetes are evolving and will continue – continuous knowledge update is a must.
• The failure of clinicians to intensify therapy when clinically indicated has been termed “clinical inertia”.
• Education and comprehensive care throughout life are the keys to good health in people with diabetes.
• Education is ‘hand holding’ the patient for life.
• Diabetes care is teamwork, turning out to be cardiometabolic, renal and vascular in approach.
• The basic minimum care team in diabetes comprises doctors, patients, dieticians, diabetes educators and nurse educators.
• The success of your diabetes management depends on:

Prevention of Diabetes Pandemic – Hope and Scope

Prof (Dr.) V. Seshiah, Chennai

• Exposure to a diabetic environment in utero is associated with increased occurrence of impaired glucose tolerance and a defective insulin secretory response in adult offspring independent of genetic predisposition to type 2 diabetes.
• A blood test may identify gestational diabetes risk in the first trimester. NIH analysis suggests early screening could allow for lifestyle changes before the condition develops. The influence of pre-pregnancy metabolic changes on fetal development may be mediated through modification of oocyte metabolism, predominantly of their mitochondria, through changing early embryonic growth and later growth trajectories.
• Primordial prevention: Ideally peak maternal postprandial blood glucose should be ~110 mg/dL from the preconception period but never cross 12 mg/dL at any time.
•  What is needed for primordial prevention?

2022 Update in Diabetes

Dr. A. K. Das, Puducherry

Nonsteroidal MRAs: A New Hope for Improved Cardiorenal Outcomes in Patients with CKD and T2D

Dr. Shashank Joshi, Mumbai

• CKD progression in T2D is driven by the combined effects of metabolic, hemodynamic, inflammatory and fibrotic factors.
• Inflammation and fibrosis are potential treatment targets to address the residual risk in CKD and T2D.
• Mineralocorticoid receptor (MR) overactivation is a major driver of kidney damage. MR overactivation, which contributes to inflammation and fibrosis, is a potential treatment target to slow CKD progression.
• Finerenone, a novel, nonsteroidal, selective MRA, blocks MR overactivation and reduces albuminuria.
• Finerenone is different from available steroidal MRAs.
• Finerenone is hypothesized to slow CKD progression and prevent CV events by directly targeting inflammation and fibrosis. FIDELIO-DKD and FIGARO-DKD results indicate that finerenone is an effective investigational treatment option for CV and kidney protection in patients with CKD stage 1-4 and T2D.

Hepatopancreatic Fat-Fetuin-A Based Axis for the Pathogenesis of Diabetes and its Reversal

Dr. Anoop Misra, New Delhi

• A number of studies have demonstrated a link between pancreatic fat and impaired glucose metabolism, as well as between pancreatic fat and T2DM. In general, pancreatic volume decreases with age and in diabetes, while pancreatic fat increases with both.
• Ethnic differences in pancreatic volume have been reported, while research in India is negligible.
• Fetuin-A is a key metabolic regulator causing effects on the pancreas and multiple other tissues, and responsible for insulin resistance, hyperglycemia and (with palmitate) β-cell apoptosis
• Different approaches, such as a hypocaloric diet, exercise, bariatric surgery and pharmacological interventions, can reduce pancreatic fat content. A decrease in pancreatic and hepatic fat and a decrease in fetuin-A (insulin resistance/ inflammation) could lead to reversal of diabetes.

Obstructive Sleep Apnea and Diabetes – The Link

Dr. Anil Bhoraskar, Mumbai

• Obstructive sleep apnea (OSA): Repeated partial or complete obstruction of the upper airway during sleep.
• The complications linked with OSA are metabolic, cardiovascular, behavioral and others such as excessive daytime sleepiness, headache and fatigue-related accidents.
• A number of studies have shown that OSA is a risk factor for T2D independent of obesity and other risk factors.
• Interestingly, both OSA and T2DM are associated with similar comorbidities such as hypertension, CVD, dyslipidemia and CKD.
• Several cross-sectional studies have demonstrated the link between OSA and poor glycemic measures. Continuous positive airway pressure (CPAP) is the gold standard treatment for OSA. Along with CPAP, lifestyle modification, sleep hygiene and weight loss should be advised in all patients with T2D with OSA.
• Some other treatment options for OSA include dental appliances, surgeries in a select group of patients, and conservative measures such as alcohol cessation, smoking cessation and mild nasal decongestants.
• CPAP reduces the risk of incident T2D. Treatment with CPAP improves HbA1c levels, fasting plasma insulin and insulin resistance. In T2DM, OSA treatment with CPAP has been shown to reduce the mean arterial pressure, systolic BP and diastolic BP.
• CPAP has been shown to delay or prevent the occurrence of CVD in T2DM patients.
• Retinopathy, nephropathy and neuropathy are probably delayed by treatment with CPAP.

Technological advancement

Are We Migrating from SMBG to CGM?

Dr. Banshi Saboo, Ahmedabad

• Self-monitoring of blood glucose (SMBG) measurements do not capture the post-meal spike while continuous glucose monitoring (CGM) captures post-meal spike and glycemic excursions across the day.
• CGMs provide information about the glucose concentration as well as trend information about the direction and rate of changing glucose concentrations.
• Guidelines recommend the use of CGM in diabetes management.
• Numerous RCTs have demonstrated benefits from using real-time CGM over SMBG, including a lower A1c and/or reduced hypoglycemia

Connected Blood Glucose Monitoring from Evidence to Clinical Practice

Dr. Banshi Saboo, Ahmedabad

Focus on TIR through CGM to Target Better Clinical Outcomes in Diabetes

Dr. Manoj Chawla, Mumbai

• There are many faces of A1c, though HbA1c is still a standard measure for glycemia, they don’t provide a complete picture.
• Ambulatory glucose profile (AGP) carries metrics data of time-in-range (TIR) and is crucial in SMBG, CGM, etc.
• % TIR and HbA1c have a broad correlation between a range of subjects, ages and technologies across 18 subjects.
• For every absolute 10% change in % TIR, there is approximately a 0.8% reduction in HbA1c along with a 6.4% risk reduction for abnormal CIMT.
• TIR and glycemic variability (GV) are mathematically interrelated; however, they are not interchangeable

Point of Illumination

Cardiovascular Outcome Trial Requirements should not be Abandoned

Dr. Rajeev Chawla, New Delhi

• The requirement to test one new drug in class should be tested in CVOT to give assurance and evidence to treating physicians about its efficacy and safety.
• It should be noted that in referring to CVD, we include not only macrovascular but also microvascular morbidity.
• Both are equally important from a CV outcome point of view.
• New and existing glucose-lowering therapies should be evaluated for their overall effects on vascular health, the various CV phenotypes (e.g., heart failure), and specific vascular complications such as amputations.
• CVOTs have sensitized diabetes care providers to the opportunities for multifactorial and comprehensive diabetes care, including CV risk reduction.
• Some of the more recent CVOTs have embraced comprehensive cardiorenal primary endpoints, originally proposed by investigators from earlier trials.
• CVOTs have still a long way to go. Primary intervention trials in lower-risk populations could determine whether diabetes medications offer CV protection for those who do not yet have CVD.

Cardio-Renal Pearls

Reducing CV Risk in People with Diabetes – Should Everyone be on an SGLT2 Inhibitor?

Dr. Miles Fisher, UK

• Diabetologists prescribe SGLT2 inhibitors owing to their action on the kidney leading to a reduction in blood glucose by glycosuria along with the benefits such as the reduced risk of MACE, CV death, all-cause death, HF hospitalization, etc. as proven by CANVAS, EMPA-REG and DECLARETIMI trials.
• RSSDI-ESI clinical practice recommendations include the initiation of T2DM treatment with metformin along with lifestyle intervention.
• However, if glucose control is not achieved, dual or triple therapy is recommended based on the use of two or three oral antidiabetic agents such as SUs, GLP-1, SGLT2 inhibitors, DPP-4 inhibitors, etc.
• Guidelines for diabetes management should be based on the level of cardiorenal risk rather than HbA1c.

Cardiorenal Metabolic Disorder, is the Panacea Available Now?

Dr. Mangesh Tiwaskar, Mumbai

• “It should be the function of medicine to have people die young as late as possible.” – Ernest L Wynder
• Diabetes treatment for CVD reduction is categorized in two arms, i.e., SGLT2 inhibitors and GLP-1R antagonists with hemodynamic effect and anti-atherogenic effect mechanism of action, respectively.
• SGLT2 inhibitors improve ventricular loading conditions (diuresis, natriuresis, etc.), myocardial energetics, TGF, IGH, etc. by modulating SNS activity.
• GLP-1R on the other hand has anti-inflammatory effects, reduces oxidative stress, inhibits RAAS, increases natriuresis, etc.
• SGLT2 inhibitors and GLP-1R provide complete CV renal protection combined and are a challenge.

Unleashing the Potential for Renal Protection with SGLT2 Inhibition: A Clinical Perspective

Dr. N. K. Singh, Dhanbad

• SGLT2 inhibitors are an important weapon in our arsenal against not only type 2 diabetes but also the conditions that we encounter that go hand-in-hand, including CKD and CVD.
• Frontline clinicians should initiate SGLT2 inhibitors for patients with type 2 diabetes and diabetic kidney disease who have an eGFR of at least 30 mL/min/1.73 m2 .
• Deferring initiation of SGLT2 inhibitors to a specialist (a nephrologist or endocrinologist) will result in a faster progression of diabetic kidney disease irrespective of glycemic control, and it is crucial to initiate these medications as early as possible.
• Prescribers should be aware of the initial reversible drop in eGFR of approximately 5 to 8 mL/min/1.73 m2 (up to a 20% drop) in the first 2 weeks after starting SGLT2 inhibitors, which is due to the hemodynamic effects of the drug.
• The use of an SGLT2 inhibitor can slow the decline in GFR, reduce the onset of microalbuminuria and slow or reverse the progression of proteinuria.

Preventing Diabetes Complications – 100 Years on from Insulin: Which of the Newer Classes will Prevail?

GLP1-RA

Prof (Dr.) Aravinda J, Bengaluru

• To tackle the diabetes-related complications the need is to enroot the cause (hyperglycemia, obesity) effectively.
• GLP-1RA from many clinical trials has proven itself as a powerful agent targeting the core underlying causes. Its potential in reducing MACE and stroke is noticeable. How can we forget how GLP-1 can improve metabolic derangement?

SGLT2 Inhibitors

Dr. Purvi Chawla, Mumbai

• SGLT2 inhibitors: durable glycemic efficacy, body weight and BP reduction with CV benefits and renoprotective action without a higher risk of hypoglycemia.
• These are multi-tasking, oral, inexpensive, antidiabetic agents, here to stay.
• There is adequate guidance to use them in newly diagnosed patients, those with multiple risk factors, prior MI, ASCVD, CKD and heart failure (reduced and preserved EF)-potentially in T1DM, prediabetes.
• Body weight lowering (kg) with the highest approved doses of SGLT2 inhibitors and long-acting GLP-1RA.
• CV outcomes in patients with T2D and CVD or high CV risk: SGLT2 inhibitors and GLP-1RAs show favorable effects on long-term CV outcome, only SGLT2 inhibitors have shown a benefit on HHF.
• In a meta-analysis of RCTs in patients with T2D and CVD or high CV risk: SGLT2 inhibitors showed a consistent beneficial effect on HHF not observed with GLP-1RAs.
• Real-world use of SGLT2 inhibitors was associated with a consistent reduction in HHF risk vs. GLP-1RAs, in patients with T2D regardless of CVD status.
• Kidney outcomes in patients with T2DM and CVD or high CV risk: SGLT2 inhibitors have shown consistent kidney benefits, including slowing of eGFR decline and reduction of hard kidney outcomes. All SGLT2 inhibitors but not all GLP-1RAs have demonstrated benefit in slowing eGFR decline over time when compared with placebo in patients with T2DM and CVD or high CV risk.
• The risk-benefit ratio has always to be assessed before prescribing.
• Adequate counseling for UTIs, GUIs and appropriate hydration should always be done. It is not to be used in contraindicated patient subgroups.

Cardiovascular Risk Factor Management and Prognosis in Patients with Dysglycemia

Dr. Jaakko Toumilehto, Finland

• The 2019 ESC Guidelines on diabetes, prediabetes and cardiovascular diseases (CVDs) has given specific recommendations on CV risk categories in patients with DM, for the use of laboratory, ECG and imaging testing for CV risk assessment in asymptomatic patients with DM, for lifestyle modifications in diabetes mellitus (DM) and pre-DM, for glycemic control in an individual with DM, for the management of BP in patients with DM and pre-DM, for the management of dyslipidemia with lipid-lowering drugs, antiplatelet therapy in primary prevention in DM.
• A few important recommendations are:
  • Moderate to vigorous physical activity, notably a combination of aerobic and resistance exercise, for ≥150 min/week is recommended for the prevention and control of DM unless contraindicated, such as when there are severe comorbidities or a limited life expectancy.
  • A Mediterranean diet, rich in polyunsaturated and monounsaturated fats, should be considered to reduce CV events. Vitamin or micronutrient supplementation to reduce the risk of DM or CVD in DM is not recommended.
  • Tight glycemic control is recommended targeting near-normal HbA1c (140/90 mmHg.
  • Lifestyle changes including weight loss if overweight, physical activity, alcohol restriction, sodium restriction and increased consumption of fruits, vegetables and low-fat dairy are recommended in patients with DM and pre-DM.
  • To manage BP in patients with DM and pre-DM, it is recommended that treatment is initiated with a combination of a renin-angiotensin-aldosterone system (RAAS) blocker with a calcium channel blocker or thiazide/thiazidelike diuretics.
  • Statins are recommended as the first-choice lipid-lowering treatment in patients with DM and high LDL-C levels: administration of statins is defined based on the CV risk profile of the patient and the recommended LDL-C or nonHDL-C target levels.
  • Lifestyle interventions (with a focus on weight reduction and decreased consumption of fast absorbed carbohydrates and alcohol) and fibrates should be considered in patients with low HDL-C and high triglyceride levels. ‹ In patients with DM at high/very high-risk, aspirin (75-100 mg/day) may be considered for primary prevention in the absence of clear contraindications.

Updates on OHA

Pharmacotherapy of Type 2 Diabetes: Getting the Basics Right to Improve Outcomes

Dr. Mandeep Bajaj, USA

• Choose an agent after considering the condition of the patient and any underlined comorbidities that he may have.
• Consider the available data with all the drugs including a GLP‑1 receptor agonist, a DPP-4 inhibitor, an SGLT2 inhibitor, pioglitazone and sulfonylurea.
• For instance – In a patient with heart failure, SGLT2 inhibitors are recommended; In a patient with nonalcoholic hepatitis, a GLP-1 receptor agonist or pioglitazone may be added.
• Base your clinical judgment on the overall condition of the patient (instead of just glycemic control), and underlying comorbidities, consider the options available and then reach a conclusion

Place of Other Oral Antidiabetic Agents in the Era of SGLT2 Inhibitor: Which, When and Why?

Dr. Vijay Panikar, Mumbai

• Macrovascular damage starts many years before the onset of diabetes.
• Insulin resistance and its complications and β-cell preservation have to be adequately addressed for positive long-term outcomes. If insulin resistance is treated right from day 1, we will see lesser macrovascular complications.
• Metformin + pioglitazone most durable, less weight gain with metformin in place.
• Add an SGLT2 inhibitor and that’s an unbeatable combination.
• Metformin + pioglitazone gives the best results – when endogenous insulin is present.
• Metformin + pioglitazone + SGLT2 inhibitors with endogenous insulin – EARLY USE = INTELLIGENT USE.

Metformin Supreme Position as a First Choice: Pros and Cons

Dr. Meena Chhabra, New Delhi

• Based on the medical community’s extensive experience and the drug’s demonstrated efficacy, safety and low-cost, metformin should remain the “foundation therapy” for all patients with type 2 diabetes, barring contraindications.
• Metformin is contraindicated in:
  • Patients with severe renal dysfunction (GFR < 30 mL/ min/1.73 m2 ).
  • Hypersensitivity to metformin and metabolic acidosis. Metformin dosing should also stop on the day of any surgery.
  • Discontinue metformin before giving iodinated contrast agents in patients with a GFR mL/min/1.73 m2 , lactic acidosis risk factors.
• Metformin may be restarted after the procedure once the patient’s GFR has normalized.
• Avoid metformin in hepatically impaired or unstable heart failure patients.
• SGLT2 inhibitors or GLP-1RA may only be considered as first-line therapy in case of ASCVD or high/very high CV risk.

Sulfonylurea in 2022: Still Standing Tall!

Dr. S. R. Aravind, Bengaluru

 The role of modern SUs in the T2DM continuum:

Gliptin, Gliflozin, Synergy

Dr. Vinod Mittal, New Delhi

• Robust/rapid HbA1c reduction – no added hypoglycaemia.
• Weight loss – fat. ‹ Decrease in SBP…Uric acid.
• Cardiorenal protection. Less GTI.
• Cost, convenience, compliance

DPP-IV and Organ Protection: Evidence-based Choices

Dr. S. K. Sharma, Jaipur

• DPP-4 inhibitors beyond its well-established actions on the pancreas GLP-1 further exert direct effects on the heart, vessels and kidneys, mainly via the GLP-1R.
• Preclinical evidence suggests that DPP-4 inhibitors may be beneficial in settings of acute renal failure and chronic kidney diseases such as diabetic nephropathy, but also cardiac diseases such as myocardial infarction and heart failure.
• DPP-4 inhibitors raise the possibility of a direct renoprotective effect independent of improvements in glycemic control.
• DPP-4 inhibitors demonstrate clinically meaningful benefits in clinical phase 3 and 4 trials in the treatment of acute kidney failure, chronic kidney failure and acute myocardial infarction as well as heart failure.

25 Years of Acarbose in India

Dr. B. M. Makkar, New Delhi

• In Indian patients considering a carbohydrate-rich diet, acarbose works by inhibiting alpha-glucosidase causing a delay in intestinal absorption of carbohydrates along with decreasing insulin need.
• The structural uniqueness of the acarbose reduces PPG via an insulin-sparing mechanism and facilitates its entry into the large intestine.
• Several studies have proved that acarbose reduces Hb1Ac by 0.8% along with a reduced risk of progression from prediabetes to type 2 diabetes.
• Acarbose is recommended by various international communities owing to glucose-lowering efficacy across a broad range of patients, regardless of BMI, HbA1c, duration of diabetes, insulin resistance, condition of β cells, age, etc.

A Silver Lining in the Armamentarium of Diabetes Therapy: The Birth of the World’s First “Peptide in a Pill”

Dr. Rajiv Kovil, Mumbai

• Peptides are challenging compounds and require engineering to optimize their in vivo performance.
• Peptide analogs can be designed to offer improved stability and prolonged t1/2, while a formulation approach can facilitate improved absorption.
• Absorption of oral semaglutide takes place in the stomach and requires coformulation with SNAC.
• The mechanism of absorption is shown to be compound-specific, transcellular and without any evidence of an effect on tight junctions.
• The development of “peptide in a pill-oral semaglutide” represents an advancement in treatment possibilities for chronic diseases by transforming injectable therapies into tablet-based oral formulations

PIONEERing the New Revolution in the Management of T2DM with Oral Semaglutide

Dr. Anil Bhansali, Chandigarh

• Oral semaglutide demonstrated significantly greater HbA1c and weight reductions vs. sitagliptin, empagliflozin and liraglutide.
• Oral semaglutide is superior compared to empagliflozin and sitagliptin in controlling HbA1c, while noninferior to liraglutide.
• Oral semaglutide has superior weight reduction properties compared to sitagliptin, linagliptin and empagliflozin.
• Cardiovascular safety: Confirmed for oral semaglutide in PIONEER 6, showing a 21% nonsignificant reduction in MACE in favor of oral semaglutide compared with placebo.
• Overall safety: Oral semaglutide was well-tolerated with a safety profile consistent with the GLP-1RA class. The most common adverse event was mild-to-moderate nausea. ‹ Efficacy was established when given early in therapy, late in therapy and regardless of renal or hepatic impairment

Debate (1)

Sulfonylureas have been Unfortunately Victimized?

YES: Dr. K. N. Manohar, Bengaluru

• Over the years, even after the evolution of the market, sulfonylureas (SUs) prescription is dominant among other oral antidiabetic agents (90.2%) with/without combination with metformin.
• According to ADA guidelines 2021, choosing a later generation SU, namely glimepiride can reduce the risk of hypoglycemia.
• CAROLINA (6.5 years) and GRADE study has shown that weight gain was insignificant, hypoglycemia was controlled, β-cell exhaustion and CVOT were controlled.
• Modern SUs are appropriate, available, affordable and accessible.

NO: Dr. Tejas Shah, Mumbai

• From SUs and metformin, the OAD has evolved to provide added benefits such as the reduced risk of CV events, renal failure, dyslipidemia, BP and all-cause mortality with a glucose-lowering effect.
• Out of 8 known pathological effects, SUs only work to regulate impaired insulin secretion.
• UKPDS, ADOPT and TOSCA trials of SUs, show favorable CV neutrality, however, LEADER, PIONEER and SUSTAIN trials show CV superiority of other OADs such as semaglutide over SUs.
• SUs have short glycemic protection, increased weight gain, increased β-cell apoptosis, etc
• At the end of the day, the treatment that provides event-free life years to the patients is preferred

Debate (2)

SGLT2 Inhibitor is 2nd Add-on for Everyone

Dr. Piyush Desai, Surat

• Over the last 5 years, several landmark trials such as EMPA-REG, CANVAS, CREDENCE, DAPA-HF and KDIGO have shown the multidimensional action of SGLT2 inhibitors in diabetes therapy and reducing the risk of CV renal outcomes.
• Based on this evidence, ADA and AACE guidelines have been changed and recommend early prescription of SGLT2 inhibitors for patients with a high risk of ASCVD, CKD, HF, etc.
• According to AACE guidelines, SGLT2 inhibitors can be used in combination with metformin, if the entry-level HbA1c is high.
• SGLT2 inhibitor is a cost-effective drug that when reduces weight and the risk of hypoglycemia along with controlling several other risk factors.

SGLT2 Inhibitor: Cons as 1st Add-on Therapy

Dr. Pravin Kalvit, Bilaspur

• Though cardiologists and nephrologists have turned over to SGLT2 inhibitors, there have been several adverse events reported such as infection of the genital, leg and foot amputation, ketoacidosis, bone fracture risk and cancer risk, etc.
• There are several don’ts with SGLT2 inhibitors such as initiation of therapy with empagliflozin/dapagliflozin in a patient with eGFR

Evogliptin

Dr. A. K. Singh, Kolkata

Dr. C. S. Yajnik , Pune says – There is a lot to learn.

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