CME INDIA Presentation by Dr N K Singh.
Based on RSSDI-2020 talk (27th November), discussing Virtual EASD (European Association for Study of Diabetes) 2020.
20 best messages from the Virtual EASD 2020.
2020 is dedicated COVID Year and all roads are leading to one direction. Still, this year has also witnessed practice changing impacts by some landmark trials. It is important to know these messages and modify the clinical practice…
1. GLP-1 Semaglutide tablet can be a cornerstone treatment for type 2 diabetes
- Semaglutide is the first FDA approved GLP-1 RA pill.
- Results from a post-hoc analysis of pooled data from 2 phase 3 trials named, SUSTAIN-6 and PIONEER-6 were presented at EASD 2020.
- It brings very important message that addition of Semaglutide on the top of standard of care is able to give 20% risk reduction in 10-year risk of experiencing cardiovascular events compared to standard of care alone. It supports in clinical decision-making for type 2 diabetes patients at high risk of developing cardiovascular disease.
- In simple way, semaglutide if added, can extend life without a cardiovascular event in patients with type 2 diabetes and high cardiovascular risk for up to 3 years, with average being 18 months.
- A post hoc analysis of the SUSTAIN 1-7 trials shows that semaglutide has the potential to improve renal function with type 2 diabetes. It has shown a marked reduction in UACR (Urinary albumin -to-creatinine ratio) and thus reduced risk of end-stage kidney disease.
- New findings in totality suggest that semaglutide has a suitable renal safety profile and has potentially reno protective effects apart from reducing the risk of MACE across the continuum of baseline CV risk in broad type 2 diabetes population.
- In a combined analysis of several trials, semaglutide and GLP-1 Liraglutide decreased the risk of stroke for people with type 2 diabetes and high risk of heart disease. The results from these trials also suggested there was a benefit of early treatment with a GLP-1 medication.
2. Primary Care Diabetes Europe (PCDE)’s new guideline for primary care physicians
- Dr. Kamlesh Khunti showed that people with early onset type 2 diabetes (diagnosed before age 40) have a 14 times greater risk of heart attack and a 30 times greater risk of stroke than people without diabetes. For these people, combination therapy is strongly encouraged.
- PDCE encouraged the use of early combination therapy (prescribing metformin with an SGLT-2 or GLP-1) instead of prescribing first one medicine, waiting until glucose levels rise, and then adding an addition medication. This approach aims to get heart-protecting medications to people early in the course of their diabetes.
- The guidelines recommend determining whether someone with type 2 diabetes has “very high cardiovascular risk,” “high cardiovascular risk,” or is “elderly/frail” to decide what treatment strategy is best for them.
- PDCE symposium at EASD has very important messages to all parts of the world. It encourages a straight use of early combination therapy for cardio-renal risk reduction by prescribing metformin with SGLT-2 Inhibitors and GLP-1 RA. This is a very aggressive approach.
3. New results of the EMPEROR-Reduced trial
- New results from EMPEROR-Reduced trial were presented and very important message emphasized on the efficacy of empagliflozin in reducing the risk of cardiovascular death and hospitalization for heart failure by 25 percent and significantly preventing the decline of eGFR, in patients with or without diabetes.
- In renal perspective, the composite outcome (chronic haemodialysis, renal transplantation, profound sustained reduction in eGFR favoured empagliflozin significantly.
- Empagliflozin is superior to placebo in improving heart failure outcomes among patients with symptomatic stable heart failure with reduced ejection fraction.
- Benefit was seen in a reduction in heart failure hospitalisations, as well as in renal outcomes.
- The findings are similar to the DAPA-HF trial for dapagliflozin.
4. Cardiovascular outcomes of patients with type 2 diabetes treated with SGLT-2 inhibitors versus GLP-1 receptor agonists in real life.
- Interestingly an observational, retrospective study comparing CV outcomes of patients receiving SGLT-2 inhibitors or a GLP-1 RA in real -world settings
- In this real-world analysis, SGLT-2 inhibitors protected from hospitalisation for heart failure more than GLP1-RAs.
- Better outcomes were seen in 3P-MACE with SGLT-2 inhibitors vs. GLP-1 RAs.
- According ADA and the EASD consensus, SGLT-2 inhibitors should be preferred over GLP-1 receptor agonists (GLP-1 RAs) in patients with a high risk of established atherosclerotic cardiovascular disease (ACVD), heart failure (HF), or chronic kidney disease (CKD) if HF or CKD predominates.
- However, this view has recently been challenged since both classes may offer benefits to reduce adverse cardiovascular (CV) events, but SGLT-2 inhibitors are preferred for patients with HF.
- The finding that better outcomes were seen in 3P-MACE with SGLT-2 inhibitors compared to GLP-1 RAs was unexpected
5. Incident cardiovascular disease by clustering of favourable risk factors in type 1 diabetes – The EURODIAB Prospective Complications Study
- This study showed that greater clustering of favourable CVD risk factors was associated with a lower risk of CVD with a significant linear trend.
- Clearly, HBA1c emerged as the most protective factor against CVD in type 1 diabetes. These findings have a significant clinical importance.
- The message is loud that targeting combined risk factors appear to be most effective in preventing CVD risk than targeting single risk factors.
6. DAPA-CKD: Dapagliflozin prolongs survival in CKD with, without type 2 diabetes
- A new floor has eGFR been set after new data from DAPA-CKD.
- At EASD virtual meeting Dr Hiddo J.L and Heerspink expressed the exciting idea about lowest level for starting SGLT2 inhibitors in everyday practice up to eGFR as low as 25 mL/min per 1.732.
- Now regulatory bodies might have to change the existing eGFR limit of 30.
- It has been shown that dapagliflozin is effective across the spectrum of renal function.
7. New VERTIS-CV data: Kidney function preserved with ertugliflozin in type 2 diabetes
- Much awaited VERTIS CV trial was first presented at ADA virtual meeting in June 2020.
- At EASD new exploratory analyses from this trial was presented.
- It showed that Ertugliflozin reduced risk for worsening renal function, dialysis or renal death in comparison with placebo in patients with type 2 diabetes patients.
- It was also associated with reduced urinary albumin to creatinine ratio in patients with albuminuria at baseline.
8. Effects of intensive risk factor management on cardiovascular autonomic neuropathy (CAN)in type 2 diabetes: findings from the ACCORD clinical trial
- Intensive blood glucose and BP interventions in T2D reduced the risk of CAN by 17% and 22%, respectively.
- Intensive glycaemic control was more effective in patients without prior history of CVD, and BP lowering was more effective in patients ≥65 years.
- However, these benefits must be weighed against increased risks and costs, and especially the excess mortality observed with intensive glycaemic control in ACCORD.
9. Once-weekly insulin efficacy similar to daily therapy in type 2 diabetes
- It is a very transformational news that once-weekly insulin ICODEC has shown significant promise in phase 2 trial which was presented at EASD 2020.
- This might change the way we treat insulin requiring type 2 diabetes.
- The glucose -lowering efficacy and safety profile have been found similar to that of once-daily insulin glargine in patients with type 2 diabetes.
- This trial has given hope as once-weekly insulin reduce the number of injections from 365 to 52 per year.
10. RESCUE Trial (Sub study)
- RESCUE trial was presented with landmark data showing more time in range (TIR) is associated with fewer microvascular complications, chronic complications in comparison with glycemic variability in type 1 diabetes.
- This trial gives a clear message that shorter TIR was associated with the presence of composite microvascular complications.
- Higher time in range was significantly associated with less microvascular complications. Half of the participants with TIR below 40% had at least one microvascular complication; in contrast, just 27% of people with TIR greater than 70% had at least one microvascular complication.
- Retinopathy was also strongly correlated with TIR. The rates of retinopathy for people with TIR below 40% were double the rates of retinopathy in people with TIR above 70%.
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