As we come to the end of the year, I wanted to pause for a moment. This is the final Mindful Wellness newsletter of 2025. Before looking ahead, I want to say thank you. It has been a meaningful year, one where we have had the privilege of helping many people improve their health, rebuild trust in their bodies, and release some of the shame that too often surrounds weight.
When I started this clinic in 2020, my goal was to practice medicine differently. I wanted to treat weight as the chronic medical condition that it is, and to offer care that was grounded in evidence, realism, and compassion.
Every year since then, science has moved quickly. And as 2025 closes, it feels clear that we are living in an unusually important moment in weight medicine.
A Milestone to End the Year, The First GLP 1 Pill for Weight Loss
This month, the FDA approved oral semaglutide, 25 mg daily, for chronic weight management. It is the first GLP 1 pill approved specifically for obesity.
In the pivotal phase 3 trial published in NEJM, participants were followed for 64 weeks. Those taking oral semaglutide lost an average of 13.6 percent of body weight, compared with 2.2 percent with placebo. That is a difference of about 11.4 percentage points.
This represents meaningful weight loss in just over one year. For many patients, the significance is not only the magnitude of weight reduction, but the route of administration. A pill lowers barriers for people who are hesitant about injections or who have limited access to them.
Understanding Side Effects and Why Dosing Matters
Side effects were similar to injectable GLP 1 therapies. Gastrointestinal symptoms were common, particularly during dose escalation. About 74 percent of participants experienced GI effects, most commonly nausea and vomiting, compared with 42 percent in the placebo group.
This highlights the importance of careful titration and medical supervision. Rushing dosing often leads to avoidable discomfort, and safe prescribing remains critical.
What We Are Watching Closely as We Enter 2026
What excites me is not only one approval. It is the depth of the pipeline and the speed at which innovation is happening.
Orforglipron
Orforglipron is a small molecule oral GLP 1 receptor agonist. In its phase 2 NEJM trial, participants were followed for 72 weeks. Depending on the dose, average weight loss ranged from about 7.5 percent at 6 mg, about 8.4 percent at 12 mg, and about 11.2 percent at 36 mg, compared with about 2.1 percent with placebo.
GI side effects were the most common and were most prominent during early dose escalation. Longer term phase 3 data will be important, but this represents a promising oral option that could expand access. Regulatory timelines suggest possible approval in 2026, pending results.
CagriSema
CagriSema combines semaglutide with cagrilintide, an amylin analog that targets appetite through a different pathway. In the phase 3 NEJM trial, participants were followed for 68 weeks. Average weight loss reached about 20.4 percent using a treatment policy analysis, and about 22.7 percent in participants who adhered closely to the protocol, compared with about 3 percent with placebo.
GI side effects were common, as expected with combination therapy. Discontinuation due to adverse events was relatively low at about 6 percent, given the significant weight loss. Novo Nordisk has indicated plans for regulatory submission in 2026.
Retatrutide
Retatrutide is a triple agonist that targets GLP 1, GIP, and glucagon receptors. In its phase 2 NEJM trial, participants were followed for 48 weeks. At the highest doses, average weight loss reached about 22 to 24 percent of body weight. This is nearly double what was considered extraordinary only a few years ago.
These are early data, and longer trials are needed to understand durability, safety, and tolerability. GI side effects were common and dose related. Discontinuation rates were higher at the strongest doses. Still, retatrutide offers a glimpse into what may be possible later in the decade, with availability expected no earlier than 2027 if trials continue positively.
Why This Moment Matters
No medication is a cure. No trial captures real life perfectly. But taken together, these data tell an important story. Weight is being treated seriously. Mechanisms are improving. Options are expanding. Personalization is becoming possible.
Every year since 2020, progress has accelerated. And finally, the broader medical system is beginning to catch up to what many of us have understood for years. This is a disease. People deserve effective, evidence based care.
What Will Not Change at Mindful Wellness
Even as medications evolve, our approach remains the same. Careful prescribing. Thoughtful titration. Long term safety over shortcuts. Compassion over shame.
As we head into 2026, I am excited not only about new therapies but about continuing to grow this practice and support more people with care that is ethical, grounded, and human.
Later this week, I will share more about our New Year offerings and ways to get started thoughtfully in the year ahead.
Thank you for being part of this community and for trusting us with your care.
