GLP-1 Medications: What the Evidence Shows

GLP-1 medications are some of the most studied drugs in modern weight care, and they have earned the attention. They also come with real tradeoffs: side effects, cost, and a need to stay on them for the long term. Here is what the large trials show, in plain terms, so you can decide whether they fit your health.

What GLP-1 medications are

GLP-1 stands for glucagon-like peptide-1, a gut hormone that helps regulate blood sugar and appetite. Medications in this class copy that hormone. They slow how fast your stomach empties, help you feel full sooner, and reduce food noise for many people.

Wegovy (semaglutide) is a GLP-1 medication. Zepbound (tirzepatide) is a GIP/GLP-1 medication, meaning it acts on a second gut hormone, GIP, as well. Both are given as a weekly injection.

How much weight people lose

In the main semaglutide trial, adults with overweight or obesity lost about 15% of their body weight on average over 68 weeks, compared with about 2% on placebo, when both groups also received lifestyle support (Wilding et al., NEJM 2021).

In the main tirzepatide trial, average loss at the highest dose was about 21% over 72 weeks, compared with about 3% on placebo (Jastreboff et al., NEJM 2022).

These are averages. Some people lose much more, and some lose much less. A small share of people in every trial did not respond well. We set expectations with you early, and we look at your progress at regular check-ins rather than waiting for a single number.

Tirzepatide versus semaglutide

A head-to-head trial compared the two in adults with obesity. Over 72 weeks, tirzepatide produced more weight loss than semaglutide, about 20% versus about 14% (Aronne et al., NEJM 2025).

That does not make tirzepatide the right choice for everyone. It is newer, it is often more expensive, and coverage varies by plan. Some people tolerate one drug better than the other. We talk through these tradeoffs with you instead of defaulting to whichever drug lost more weight on average.

Benefits beyond the scale

The heart data are some of the strongest evidence for this class. In adults with type 2 diabetes, semaglutide lowered the risk of major cardiovascular events in an earlier trial (Marso et al., NEJM 2016).

A later trial enrolled adults with obesity and existing heart disease but no diabetes. Semaglutide lowered the rate of heart attack, stroke, and cardiovascular death by about 20% compared with placebo (Lincoff et al., NEJM 2023).

Weight loss can also improve blood pressure, blood sugar, and other markers we track. These benefits are one reason we look at the whole picture, including your labs, before recommending treatment.

Side effects and what happens if you stop

The most common side effects are stomach related: nausea, vomiting, diarrhea, and constipation. They tend to show up when you start or raise the dose, and they often ease with time. Starting low and increasing slowly helps. Less common but serious risks exist, including gallbladder problems and pancreatitis, and these medications are not right for everyone. We review your history before you start.

Stopping is the part many people do not expect. In the year after semaglutide was stopped in the trial extension, participants regained about two thirds of the weight they had lost (Wilding et al., Diabetes Obes Metab 2022). Obesity behaves like other chronic conditions in this way: the treatment works while you take it.

That does not mean you must stay on a medication forever. It means we plan the long game with you, including food, strength training, sleep, and a clear approach if you decide to stop.

What the trials leave out

Trial participants get close follow-up, free medication, and structured lifestyle support. Real life is messier. Supply gaps, prior authorization, missed doses, and dose changes all affect results, so your outcome may differ from the averages above.

Trials also run for a limited time. Most of the long-term safety data we have comes from a few years of follow-up, so we stay honest about what is still unknown. If a claim sounds bigger than the trials support, we say so.

Another point worth knowing: some of the weight lost on these medications is lean mass, not just fat. That is one reason we pair treatment with enough protein and strength training, and why we watch how you feel and function, not only the number on the scale.

What a visit looks like

You meet with us by video, on an appointment that fits your schedule. We review your weight history, medications, family history, and recent labs, and we order any tests we need, such as A1C, cholesterol, and a metabolic panel. If a GLP-1 or GIP/GLP-1 medication fits, we explain the starting dose, how we raise it, and what to do if side effects show up. We then check in on a regular schedule and adjust the plan as you go.

Is a GLP-1 medication right for you

These medications tend to make the most sense for adults with obesity, or with overweight and a related condition such as high blood pressure, prediabetes, or sleep apnea. They are not a fit for everyone, including people who are pregnant or planning pregnancy, or who have certain personal or family histories that we screen for.

The decision comes down to your goals, your health history, your labs, and what your plan covers. We walk through each of those with you.

Next step

If you want to know whether a GLP-1 or GIP/GLP-1 medication makes sense for you, start with a visit. We see you by video, review your history and labs, and build a plan you can sustain. Learn more about endocrinology care at Stonewood. Most major plans are accepted, including Medicare. Primary care should not be something you buy on top of the coverage you already pay for.