The arrival of incretin mimetics — particularly GLP-1 and dual GLP/GIP analogues — has transformed the treatment landscape of obesity. For the first time, we have therapies that deliver substantial and sustained weight loss beyond the reach of lifestyle modification or older pharmacotherapies. These agents represent a revolution in the field. Yet, their promise risks being undermined by a rigid, guideline-driven approach to prescribing that overlooks the importance of individualized care.
Current practice often follows a templated path: Escalate the dose every four weeks until reaching the “target” or “maintenance” dose endorsed by clinical trials and guidelines. While standardized dosing regimens simplify prescribing and reflect trial design, they fail to account for the lived experiences of patients.
Not every patient needs the highest marketed dose. For some, significant weight loss and metabolic benefit can be achieved at lower doses. Others experience intolerable gastrointestinal adverse effects when escalated too aggressively, leading to discontinuation. In practice, rigid titration schedules risk turning a groundbreaking therapy into an unnecessarily burdensome one.
Perhaps more concerning is the lack of proactive management of adverse effects. Nausea, reflux, constipation, and abdominal discomfort are well recognized with incretin therapy, yet many clinicians adopt a passive approach waiting for patients to complain rather than anticipating and mitigating these symptoms.
Simple strategies can improve tolerability and adherence:
- Using proton pump inhibitors for patients with reflux or persistent nausea
- Initiating gentle laxatives, hydration strategies, and dietary guidance to manage constipation
- Slowing or pausing dose escalation rather than adhering blindly to a schedule
- Recognizing that “lowest effective dose” should guide therapy, not “highest tolerated dose”
These measures not only preserve adherence but also empower patients to continue benefiting from these life-changing therapies.
Obesity is a chronic, relapsing disease with diverse presentations. Our therapeutic approach should reflect that reality. The art of medicine lies in tailoring care to the patient in front of us — not simply following a protocol. Incretin mimetics demand a shift in mindset: from rigid escalation to thoughtful personalization.
Guidelines should be seen as a framework, not a box. Clinicians must take ownership of titration decisions, adjust dosing to the individual, and proactively manage side effects. By doing so, we can maximize both efficacy and tolerability, ensuring these powerful agents reach their true potential.
The incretin revolution is here, but its success depends not only on the molecules themselves but on how we use them. If we remain confined to the guideline box — escalating doses mechanically and ignoring proactive side effect management — we risk losing patients to avoidable intolerance and disengagement.
It is time to bring flexibility, foresight, and personalization back into obesity care. Only then can we fully realize the transformative promise of GLP-1 and GIP analogues.
How do you decide when to step away from the guidelines? Share in the comments.
Dr. Madhu Pamganamamula is an internist in Odessa, TX, and is affiliated with multiple hospitals in the area, including Medical Center Health System and Odessa Regional Medical Center. He received his medical degree from Osmania Medical College NTR UHS and has been in practice 30 years. He specializes in preventive medicine, sleep medicine, and obesity and weight management (primary care) and is experienced in hypertension, sleep medicine, osteoporosis, obesity and weight management, and internal medicine.
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