Doubting that the doctor gave her wrong medicines, she first considered shifting to ayurveda or homeopathy. Finally, she decided to switch to another physician. Following consultations and tests, her new doctor substituted a medicine. Rao was prescribed Glycomet 500 mg (metformin), a widely used medicine regarded as the gold standard of first-line treatment for type-2 diabetes, instead of Dapaturn. Stamlo was not changed. Rao says the second doctor told her that Dapaturn was not ideal for her condition and the blackout might have been caused due to an unexpected drop in her blood glucose level. Since then, Rao says her blood glucose has been stable and blood pressure is in the normal range.
A quick trick question: which doctor was right? The first who gave her Dapaturn, or the second who prescribed Glycomet? Seen from different lenses, none of the two experts can be faulted.
Two Types for Type-2
Here is the catch: they were following the treatment guidelines for type-2 diabetes as recommended by separate bodies of medical experts.
The first doctor followed universally accepted guidelines, while the second was aligned to the Indian school of experts. Seeing an odd or adverse reaction, patients often panic and rush to seek a second opinion. For millions of patients, things may go awfully wrong at this juncture. Doctors, for their part, go with their experience and on the basis of how patients respond. As the number of diabetics surge in India, many doctors hardly counsel the patients on expected drug reactions. In its 2022 clinical practice recommendations, the Research Society for the Study of Diabetes in India (RSSDI), one of the largest bodies of endocrinologists and diabetes practitioners, says metformin is the first-line oral anti-diabetes drug, especially in elderly and obese patients. Its series of treatment options include drugs such as meglitinides, pioglitazone, DPP-4 inhibitors (also known as gliptins), sulfonylureas and oral GLP-1 RA for obese diabetics. GLP-1 drugs like Ozempic, Wegovy (semaglutide), Zepbound and Mounjaro (tirzepatide) are becoming wildly popular across the world for their significant weight-loss benefits in diabetes patients, who also suffer from excess weight or obesity. One of the options on RSSDI’s list is sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors)—drugs that were launched about a decade ago—and stand out for significant benefits in preventing cardiac- and kidney-related issues. Clearly, the second doctor whom Rao consulted followed the RSSDI guidelines. But her first doctor was probably more up-todate with international guidelines. Last year, experts published studies that showed preference for early treatment with SGLT2 drugs, given its advantage of cardio-renal risk reduction.
Metformin has lost the crown but not all doctors have come to terms with that dramatic shift, and some even see it as a risk. Until 2022, the American Diabetes Association along with its European counterpart, the European Association for the Study of Diabetes (EASD), had firmly placed metformin as the first-line drug for diabetes, based on its efficacy profile. SGLT2 inhibitors stood next, followed by DPP-4 medicines and then a range of other medicines are listed.
Awadhesh Kumar Singh, chief diabetologist, GD Hospital & Diabetes Institute in Kolkata, says SGLT2 is best suited as a firstline anti-hyper glycaemic in the management of type-2 diabetes for Indians.
He says the world has moved to accepting SGLT2, but India lags and that needs to change. SGLT2 drugs work by preventing kidneys from reabsorbing glucose and draining out excess sugar through urine. Meanwhile, metformin works by reducing the glucose released by liver and the amount that is absorbed from food. Referring to the specific case of Rao, Singh says a drop in glucose levels is not an exception as there may have been other underlying issues that needed to be analysed before the patient was put on the SGLT2 drug.
Last year, in a paper published in the Journal of the Association of Physicians of India, Singh along with a few leading Indian experts like Anoop Misra, V Mohan and Sanjay Agarwal said SGLT2 drugs have been used for almost a decade and have proven to be effective in managing type-2 diabetes, while their cardio- and renal-protective features make them very useful in managing patients with risk of multiple comorbidities.
The study compared SGLT2 drugs with metformin and concluded that the latter showed no beneficial effects in heart or kidney function. Singh says metformin has a role to play due to its glucose-lowering property, but adds that doctors are emotionally attached to the drug because, first, it is cheap (costs around `1 per tablet against a minimum `8 for an SGLT2 tablet) and, second, it is backed with decades of data. A cost-benefit analysis conducted by Singh, however, found that the overall economic benefit of using SGLT2 drugs exceeds that of metformin.
Meanwhile, USV’s Glycomet GP (metformin + glimeperide) clocked sales of `795 crore for the last 12 months, second highest for any pharmaceutical product in the Indian market, after GSK’s antibiotic drug Augmentin.
While it is important to have glucose under control, Singh says it is also critical to save patients from cardiac and kidney complications that are commonly associated with diabetes Unlike in the US or Europe, he says, in India medicines are not routinely reviewed, and guidelines are not followed by doctors .
“Everything is based on anecdotal observations of the doctor who relies on his or her assessment than trusting scientific evidence,” he says.
“It is not mandatory to stick to guidelines as they are only seen as recommendations. Experienced doctors say they know better than others since they have seen so many patients. That is the reason why we lag US and Europe in research. They have set the prescription norms and keep disease-wise registries to understand trends,” he adds.
Rajiv Kovil, a Mumbaibased diabetologist, points to the lack of long-term epidemiological data on Indian patients, and says we are not fully aware of the threshold at which organ damage starts due to high blood sugar.
“We do not know whether the retina is the most sensitive indicator of uncontrolled blood sugar,” he says.
Changing criteria:
The diagnostic criteria for diabetes have seen significant changes. For example, fasting blood sugar threshold for diagnosing diabetes was reduced from 140 mg/dL to 126 mg/dL a few years ago. This adjustment, says Kovil, is based on research identifying the retinopathy threshold of hyperglycaemia, where the risk of developing retinopathy increases significantly when fasting blood sugar exceeds 126 mg/dL.
Kovil says the guidelines for managing diabetes, blood pressure and high cholesterol have evolved based on robust scientific and epidemiological evidence.
“This evolution ensures that the latest research findings and population health trends are integrated into clinical practice,” he adds. As with diabetes, for dyslipidaemia (abnormal levels of lipids in blood), an LDL cholesterol level of more than 100 mg/dL is recognised as a critical inflection point.
Beyond this level, the risk of cardiovascular disease increases substantially. The approach to managing dyslipidaemia emphasises the importance of LDL size, especially in certain populations. Kovil says Indians often exhibit a “thin fat” phenotype (observable physical properties) with excess visceral adiposity (high body fat or obese), which contributes to a higher occurrence of small dense LDL particles that build up in arteries. Therefore, the LDL particle size may be more relevant than the absolute number for this group.
The threshold for blood pressure or hypertension diagnosis has also been standardised. A blood pressure reading of 140/90 mmHg is the widely accepted cut-off. Kovil says unlike BMI cut-offs for obesity, which have regional differences, the diagnostic thresholds for diabetes, blood pressure and cholesterol are consistent across different regions and racial groups.
However, the next step, when medicines are chosen, is based on the examination of patients by doctors. In the case of lipid management, Kovil says there are serious disparities depending on ethnicity. “Indians and other East Asians have distinct lipid profiles compared with Caucasians. High triglycerides, while not considered a major cardiovascular risk factor in Caucasians, can pose a significant risk in East Asians and Indians,” he says.
Additionally, he says, low HDL (high-density lipoprotein) cholesterol, prevalent in about 85% of Indians, is a well-established cardiovascular risk factor in Caucasians. The typical atherogenic (tending to promote fat in arteries) dyslipidaemia pattern in South Asians includes a modest increase in LDL cholesterol and total cholesterol, low HDL cholesterol and very high triglycerides.
Therefore, the treatment guidelines, he says, should be based on regional studies for tailored disease management for diabetes, hypertension and dyslipidaemia. Meanwhile, on August 5, the Association of Physicians of India (API), in collaboration with the Indian College of Physicians (ICP), released guidelines for the management of hypertension in patients with diabetes. API and ICP say the guidelines address the pressing need for a detailed, region-specific protocol to manage the growing dual burden of hypertension and diabetes in India.
The guidelines advocate the integration of lifestyle modifications recommending yoga as an adjunct therapy to enhance outcomes. It lays specific emphasis on multiple methods to detect and measure hypertension, including blood pressure monitoring at home. It also recommends a dual therapy, combining angiotensin receptor blockers (ARBs) with newer calcium channel blockers (CCBs) like cilnidipine. While global guidelines provide a framework for managing hypertension and diabetes, Jyotirmoy Pal, API presidentelect for 2025, says Indian and Southeast Asian populations differ significantly from Western populations in terms of ethnicity, clinical challenges and drug responses.
In his Mumbai clinic, Debashis Das, a diabetes expert, faced a puzzle when a 37-year-old came to him with chronic gastrointestinal issues. The patient had tried almost all old and new antacid drugs but got no relief. Finally, he reached out to Das, who stopped all medicines, discussed the issues and put him on a serious dietary routine and lifestyle modifications. Das is convinced that doctors need to give time for counselling their patients while following stage-wise treatment guidelines. “It is too early to say if my patient is responding but the relief is he is not getting worse,” Das says with a passing smile.
