New Era in the Management of T2DM & Obesity presented by Dr. M Davies

Updates by Dr. Jothydev Kesavadev

Dr. Jothydev Kesavadev provides comprehensive updates on advancements in diabetes management at a conference, focusing on both type 1 and type 2 diabetes.

It is important to address obesity alongside diabetes, for prevention of complications and improvement of quality of life as primary objectives. There is a need for a multifaceted approach, incorporating lifestyle modifications, medications, and potentially surgical interventions to achieve optimal outcomes.

The Effect of Weight Loss on Co-morbidities

  • 5% weight loss can reduce high blood pressure medication and aid in preventing diabetes and PCOD.
  • 5 to 10% weight loss prevents cardiovascular disease, urinary stress incontinence, and improves metabolic dysfunction.
  • 10 to 15% weight loss can lead to diabetes remission and reduces overall mortality risk.


Obesity Treatment Gap with New and Combination Pharmacotherapy

Dr. Jothydev Kesavadev emphasizes Lifestyle Modification and Medications plays a major role along with Diet.

But there are subgroup of individuals opting for interventions like gastric bypass or banding.

Melanie Davis addresses the need to fill the gap before such interventions, focusing on newer options like combination pharmacotherapy, particularly GLP-1 medications. GLP-1 drugs, originally approved for diabetes and related conditions, are now also approved for managing obesity, offering a heterogeneous range of treatment options.

  • GLP-1 receptors are present in various tissues throughout the body, including the brain, heart, and kidneys, resulting in multiple actions.
  • GLP-1 reduces appetite and food intake, increases insulin secretion, lowers glucose levels, and slows gastric emptying.
  • When combined with GIP (glucose-dependent insulinotropic peptide), the nausea side effect of GLP-1 is reduced, and it offers additional benefits such as increased insulin secretion and reduced gastric acid secretion.
  • Glucagon agonism also reduces appetite and food intake, increases insulin secretion, and enhances energy expenditure.
  • GLP-1 has demonstrated cardioprotective effects, while other molecules are undergoing clinical trials for similar benefits.

A new era is on the horizon for type 2 diabetes treatment.

  • In the pipeline, there are promising GLP-1 and combination injectables such as Orforglipron (a non-peptide), Cagrisema, Mardutide, Survodutide, and Retatrutide, currently undergoing Phase 3 clinical trials.
  • Multiple clinical trials like SYNCHRONIZE-CVOT, TRIUMPH, REDEFINE, ACHIEVE, ATTAIN, REIMAGINE, SURPASS, DREAMS will significantly impact the management of obesity and diabetes.


NEURAL-NET ARTIFICAL PANCREAS presented by Boris Kovatchev

Dr. Jothydev Kesavadev explains how Automated Insulin Delivery (AID) is now integral to the clinical practice of Type 1 diabetes (T1D) with emergence of a Neural-Net Artificial Pancreas (NAP), encoding AID algorithm into a neural network that approximates its action.

In a study, the UVA model-predictive control (UMPC) algorithm was converted into a NAP, which was then compared with UMPC in a randomized crossover trial involving 17 T1DM patients, aged 22-68, with baseline HbA1c ranging from 5.4% to 8.1%.

Results showed that the neural network implementation of UMPC demonstrated comparable performance to traditional UMPC but required significantly fewer computational resources. This process, known as NAPing, allows for the replication of insulin dosing rules using neural networks.

Furthermore, NAP calculations were approximately six times faster than UMPC, showcasing the efficiency and potential of neural network-based AID algorithms in diabetes management.


Update on Surpass-6 Trial Testing Tirzepatide vs Lispro to Further advance Basal Insulin Therapy in T2DM presented by Julio Rosenstock

Updates by Dr. Purvi Chawla

Dr. Purvi Chawla highlights that Glucagon like peptide-1 receptor agonists (GLP-1 RAs) are recommended as the first injectable therapy for type 2 diabetes mellitus (T2DM). However, despite this recommendation, basal insulin remains widely preferred due to factors such as cost, reimbursement issues, and prescribing habits.

Clinical trials like DURATION-7, AWARD-9, SUSTAIN-5, and PIONEER-8 have indeed demonstrated significant reductions in HbA1c levels when combining GLP-1 receptor agonists with basal insulin. The reduction in HbA1c ranged from 1% to 1.8%, with the highest reduction achieved by Semaglutide.

Additionally, across these same trials, there has been a significant reduction in body weight ranging from 1 kg to 6.4 kg. The highest weight reduction was observed with Semaglutide 1 mg administered once weekly.


ADA 2024 Recommendations on Advancing Basal Insulin

Dr. Purvi Chawla discusses the ADA 2024 recommendations on advancing basal insulin emphasize the importance of optimizing therapy for patients with diabetes. Despite the challenges in initiating insulin therapy, it is crucial to address poor glycemic control, which affects nearly 50% of patients.

a. According to the ADA, patients may already be on a background of metformin with or without SGLT2 inhibitors when considering initiating basal insulin.

b. If patients fail to achieve fasting plasma glucose targets with basal insulin or if the basal insulin dose exceeds 0.5 units per kg per day without achieving control, therapy needs to be intensified.

c. The ADA does not recommend switching to pre-mixed insulins but suggests several options for intensification:

  • Addition of prandial insulin: Initiate with mealtime insulin and adjust dosing according to algorithms.
  • Transition to a complete basal-bolus regimen
  • Addition of GLP-1 RA/GIP-GLP-1 RA
  • Switching to fixed-ratio combination or co-formulations


SURPASS-6 Summary

Dr. Purvi Chawla summarizes the SURPASS-6 Trial. SURPASS-6 Trial compared patients with T2DM who were uncontrolled on baseline oral hypoglycemic agents (OHAs) plus basal insulin.

They were randomized to receive either Tirzepatide at three doses (5, 10, or 15 milligrams once weekly) or a complete basal-bolus regimen with insulin lispro, while continuing oral agents and basal insulin.

In Conclusion:

  • Tirzepatide significantly improved HbA1c compared with Lispro
  • Tirzepatide groups lost an average of 10kg Body Weight
  • Rates for clinically significant hypoglycemia were 10-fold lower for Tirzepatide vs. Lispro
  • Tirzepatide improves patient related outcomes including physical and mental scores


IDF Position Statement on the 1-hour Post-load Plasma Glucose for the Diagnosis of Intermediate Hyperglycemia and Type-2 Diabetes presented by Michael Bergman

Dr. Purvi Chawla explain how the present analysis demonstrates that the plasma glucose levels associated with the best individual combination of insulin sensitivity and glucose sensitivity that are substantially lower than the conventional thresholds for FPG and 2-hG and that subjects with non-Opt glycemias are at increased risk of progressing to diabetes.

The IDF’s approach involves a mathematical solution utilizing a constraint optimization algorithm to identify minimal glucose levels associated with optimal combinations of insulin sensitivity and beta cell function. The optimized fasting glucose levels suggested are <87 mg/dL for women and <89 mg/dL for men under 45 years of age, with slightly higher thresholds for older individuals. Additionally, the optimized 2-hour glycemia levels are found to be lower than conventional diagnostic thresholds. Individuals with non-optimized glycemia are deemed to be at increased risk of progressing to diabetes.

Studies, such as the San Antonio Heart Study and meta-analyses, have demonstrated that a one-hour post-load glucose level of at least 155 mg/dL predicts the risk of diabetes more sensitively than other measures such as fasting or two-hour post-load glucose levels or HbA1c. The proposed use of one-hour post-load glucose levels for identifying high-risk individuals before the onset of conventionally defined pre-diabetes could enable more proactive lifestyle interventions to prevent the progression to diabetes.