GLP-1 Diet: What differs by drug type? Injection or oral medication—how the rate of weight loss changes with dosage

GLP-1 diet medications include liraglutide (daily injection), semaglutide (weekly injection), semaglutide (daily oral), and tirzepatide (which acts on two hormones). The rate of weight loss varies by drug type and dosage[1][2]. In pooled analyses of trials in people with obesity, a higher dose of tirzepatide was easiest to reduce weight with, but higher doses also increased gastrointestinal side effects and discontinuation rates[3]. Which is right for you depends on the amount you want to lose, your underlying medical conditions, whether you dislike injections, and whether you can sustain treatment[3].

Daily injection versus weekly injection: what is the difference?

The difference is the length of time the drug continues to work in your body. The half-life is about 13 hours for liraglutide and about 7 days for semaglutide[1]. For this reason, liraglutide requires daily injection and semaglutide requires weekly injection[1].

Tirzepatide acts not only on GLP-1 but also on GIP, another intestinal hormone[1]. Its mechanism of action on both of these is thought to lead to greater ease of weight loss[3].

How much does weight loss differ by drug and dosage?

Dosage often makes a larger difference than the drug name itself. In pooled analyses of trials in people with obesity without diabetes, the percentage of weight lost compared to placebo was 18.08% for tirzepatide 15 mg, 14.93% for 10 mg, 11.78% for semaglutide 2.4 mg, and 11.49% for tirzepatide 5 mg[3].

In other words, even at a lower dose, tirzepatide was comparable to semaglutide 2.4 mg[3]. In studies of people with diabetes, semaglutide reduced weight by an average of 6.08 kg more than liraglutide, and tirzepatide reduced weight 3.78 kg more than semaglutide[4].

However, there are still few head-to-head trials comparing these drugs, and it is said a definitive answer about which is best cannot yet be given[3][4].

In actual clinical practice, is weight loss comparable to that seen in trials?

Weight loss is often smaller than in trials. In trials, weight is reduced by 5–18%, but in actual clinical practice the reduction is somewhat smaller, as reported[5].

When comparing 6-month records in actual clinical practice, tirzepatide reduced weight by 7.0% and semaglutide by 3.4%[6]. However, in people with diabetes, the difference between the two drugs was not clear[6].

In records of 1009 people using liraglutide, 76.4% lost 5% or more of body weight, and 40.9% lost 10% or more[7].

How does oral medication compare to injection?

It is an option for those who dislike injections, but weight loss is modest. In a study where 93 people without diabetes continued oral semaglutide 14 mg for one year, those who continued lost an average of 5.7% (5.9 kg) of body weight[2].

The amount of weight loss varies widely among individuals, and this 14 mg dose was originally registered for diabetes treatment[2]. In studies, weight loss is thought to be smaller than with tirzepatide or injection semaglutide 2.4 mg[2].

How do side effects and sustainability differ?

All drugs commonly cause gastrointestinal symptoms such as nausea[4][7]. Higher doses increased both gastrointestinal side effects and the rate of discontinuation due to side effects[3].

In records of 1009 people using liraglutide, 48% experienced some side effect[7]. Serious side effects such as pancreatitis (pancreatic inflammation), bowel obstruction, and gallbladder inflammation occurred in less than 1%[7]. The most common reason for discontinuation was not side effects but medication cost (42.6%)[7].

To maintain the weight loss, the medication must be continued. When stopped, weight returns gradually, and it has been reported that in actual practice between one-half and two-thirds of people discontinued within one year[8].

What if surgery or anesthesia is planned?

GLP-1 medications slow the passage of food from the stomach[1]. For this reason, special precautions are required before surgery or procedures requiring anesthesia, and professional societies have published guidance on management[1].

If you are planning cosmetic surgery or other procedures, you must inform your surgeon that you are using a GLP-1 medication.

What should a medical consultation confirm about which drug is right for you?

It is recommended that the balance between efficacy and side effects be determined together with your physician based on your own preferences and underlying medical conditions[3]. Points to confirm are your target weight loss amount, your underlying medical conditions and current medications, whether you prefer injection or oral medication, and for how long and at what cost you can continue treatment.

The figures presented here are mainly from studies in people with obesity or overweight[3][6]. Since the same results are not guaranteed in people who want to lose only a small amount of weight, make your decision after having your physical condition evaluated by a physician.