New ‘weight-loss' drugs have lower impact in real life compared to clinical trial results: study

A recent study done in the U.S. showed that semaglutide and tirzepatide — injectable GLP-1 drugs for obesity — produce lower weight loss in a real-world setting, than during the clinical trial, because patients discontinue treatment or use lower maintenance dosages.
The results were published by researchers from the Cleveland Clinic, Ohio, U.S., in the peer-reviewed journal Obesity on June 10. Semaglutide and tirzepatide are FDA-approved medications for the treatment of type 2 diabetes and chronic weight management and are now also available in India.
Hamlet Gasoyan et al accessed electronic health record data from a large health system in Ohio and Florida to identify adults with overweight or obesity without type 2 diabetes who started with injectable semaglutide or tirzepatide between 2021 and 2023. They recorded early discontinuation (within 3 months) and late discontinuation (within 3–12 months) along with weight reduction. The researchers observed that treatment discontinuation and use of lower maintenance dosages might reduce the likelihood of achieving clinically-meaningful weight reduction in patients on these drugs.
Researchers also identified the factors associated with higher odds of achieving a weight loss of 10% or more, after one year of treatment — continuing medications or discontinuing late (vs. early), taking a high maintenance dosage, getting tirzepatide (vs. semaglutide) and were female (vs. male).
Commenting on the results of the study, V. Mohan, senior diabetologist, and chairman, Dr. Mohan's Diabetes Specialties Centre, Chennai, who has initiated patients on weight-loss drugs, says: 'The findings are not surprising because in a randomised clinical trial (RCT), there is constant follow up with the participants to continue with the drug regimen. On the other hand, in the real world, especially if patients buy their own medication, they often stop the drug. Even otherwise, compliance rates in real world are much poorer than in an RCT. The bottom line is that these drugs work as long as they are taken. That is how it is with most drugs, if you stop statins, for instance, cholesterol levels go up; if you stop anti-diabetic drugs or BP drugs, the sugar and BP go up.'
'A reality check'
Anoop Misra, who heads Fortis C-DOC Hospital for Diabetes and Allied Sciences in Delhi, who has also put his patients on these class of drugs, says: 'This study gives us a reality check of weight loss and blood sugar lowering effects of these drugs. It is important to note that discontinuation of such drugs is likely to be more in India, driven also by cost concerns. Non-compliance to diet and exercise are additional reasons to be considered in India which may cause lower weight loss.'
'Our findings about the real-world use patterns of these medications and associated clinical outcomes could inform the decisions of healthcare providers and their patients on the role of treatment discontinuation and maintenance dosage in achieving clinically meaningful weight reductions,' said Dr. Gasoyan.

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