Today October 4 is the second birthday of my dear granddaughter Anushka, so a very Happy Birthday to Anushka Baba.


India has a huge burden of patients with diabetes, there were about 77 million in 2019. The highest prevalence state wise was 13.6% in Chandigarh, with Tamil Nadu having 10.4% and Punjab 10%. Delhi had a prevalence of 26% and Chennai 22%.


Metformin is unanimously considered the first choice in treating type 2 diabetes, and recent randomised cardiovascular outcome trials have shown effectiveness of SGLT2 inhibitors and GLP receptor agonists in improving clinical outcomes. These studies were done in patients with established cardiovascular disease or risk factors.


Treatment of low risk diabetes patients however remains unclear. The GRADE trial attempts to fill the gaps. The trail included more than 4000 patients already on metformin, who had onset of diabetes in the last 10 years. Four classes of drugs were added to metformin. Insulin glargine (long acting), a sulfonylurea namely glimepiride, a GLPR agonist , or a DPP4 inhibitor namely sitagliptin. At base line glycated haemoglobin ranged from 6.8 to 8.5%. The aim in treatment of diabetes is achieving a glycated haemoglobin below 7%.


At an average follow up of 5 years adding insulin glargine to a GLP R agonist was more effective in reducing glycated haemoglobin. Sitagliptin was the least effective in reducing glycated haemoglobin. Hypoglycemia was most at 2.2% with glimepiride. Microvasular complications ( retinopathy, nephropathy, neuropathy ) were similar, but liraglutide reduced cardiovascular outcomes by 29%.


A limitation is that an SGLT2 inhibitor was not included because this class of drug was not approved by the FDA when the GRADE trial began.


The take home message is that in a low risk patient with diabetes begin treatment with metformin, and then add an SGLT2 inhibitor or a GLPR agonist or if need be a long acting insulin.


Importantly a sulfonylurea like glimepiride would also be effective in controlling glycated haemoglobin level. 


All these drugs are available in India at a very reasonable price.


But diabetes is a progressive disease as the GRADE trial has shown with almost 70% pf patients having a glycated haemoglobin above 7% at 5 years.

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