Semaglutide: Dosing, Weight Loss Results, Side Effects, and How It Compares to Tirzepatide

What semaglutide is and which products are approved

Semaglutide binds and activates the receptor for glucagon-like peptide-1, a natural hormone that helps regulate appetite and calorie intake and stimulates insulin release in a glucose-dependent way [3][1]. The labels describe GLP-1 receptors in brain regions that regulate appetite, and semaglutide also delays gastric emptying [3]. It is a GLP-1 analogue with 94% sequence homology to human GLP-1 and a half-life of about 1 week. Wegovy injection is administered once weekly [3].

The approved semaglutide products differ in use and dosing:

• Ozempic injection (approved 2017-12-05) is for glycemic control in adults with type 2 diabetes, to reduce major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease, and to reduce kidney outcomes in adults with type 2 diabetes and chronic kidney disease [6][1].
• Rybelsus tablets and Ozempic tablets are for type 2 diabetes and for cardiovascular risk reduction in adults with type 2 diabetes at high risk of these events [2][7].
• Wegovy injection (approved 2021-06-04) is for weight reduction in adults and children aged 12 and older with obesity, cardiovascular risk reduction in adults with established cardiovascular disease and obesity or overweight, and noncirrhotic MASH with moderate to advanced fibrosis [8][3].
• Wegovy tablets (25 mg, approved 2025-12-22) carry the cardiovascular and weight indications for adults only [9][3].

Ozempic has no weight-loss indication [1]. The Wegovy label does not recommend combining Wegovy injection or tablets with another semaglutide-containing product or any other GLP-1 receptor agonist [3].

Dosing: how each semaglutide product is started and escalated

Wegovy injection: the label starts at 0.25 mg weekly for weeks 1 to 4, then 0.5 mg for weeks 5 to 8, 1 mg for weeks 9 to 12 and 1.7 mg for weeks 13 to 16, with maintenance from week 17 [3]. For weight reduction in adults it gives 2.4 mg weekly as the recommended dose and 1.7 mg as the alternative, and allows a maximum of 7.2 mg weekly for adults who tolerate 2.4 mg for at least 4 weeks and need more weight loss; the pediatric maximum is 2.4 mg [3]. The Wegovy label describes a missed-dose approach: a missed injection may be taken when the next scheduled dose is more than 2 days away, and after 2 or more consecutive missed doses the label says to re-escalate from a lower dose [3].

Ozempic: the label starts at 0.25 mg weekly for 4 weeks, which it describes as not a maintenance dose, then 0.5 mg [1]. It allows increases to 1 mg and then 2 mg only after at least 4 weeks on the current dose, with a maximum of 2 mg weekly, and says a missed dose is given within 5 days or skipped [1].

Tablets follow different schedules in their labels. Rybelsus uses 3 mg for 30 days (not effective for glycemic control), 7 mg for days 31 to 60, then 7 or 14 mg; Ozempic tablets use 1.5 mg, then 4 mg, then 4 or 9 mg [2]. The labels say to take both on an empty stomach with up to 4 ounces of water, swallowed whole, with at least 30 minutes before food, drink or other oral medicines, and that the two products are not substitutable mg for mg [2]. The Wegovy tablet label uses 1.5 mg for days 1 to 30, 4 mg for days 31 to 60, 9 mg for days 61 to 90, then 25 mg from day 91 [3].

How much weight loss does semaglutide produce?

STEP 1 enrolled 1,961 adults with a BMI of 30 or higher, or 27 or higher with a weight-related condition, and no diabetes. Over 68 weeks, semaglutide 2.4 mg weekly plus lifestyle intervention produced a mean weight change of -14.9% versus -2.4% with placebo, a difference of 12.4 percentage points [4]. Weight loss of at least 5% occurred in 86.4% versus 31.5%, at least 10% in 69.1% versus 12.0%, and at least 15% in 50.5% versus 4.9% [4].

Weight loss is smaller in people with type 2 diabetes. In STEP 2, 1,210 adults with type 2 diabetes and a BMI of 27 or higher lost 9.6% of body weight on semaglutide 2.4 mg versus 3.4% on placebo at 68 weeks [10]. In STEP 5, 304 adults without diabetes were followed for 104 weeks and lost 15.2% versus 2.6% on placebo [11].

Higher and oral doses have been tested. In STEP UP, 1,407 adults with obesity and no diabetes lost 18.7% on 7.2 mg weekly, 15.6% on 2.4 mg, and 3.9% on placebo at 72 weeks [12]. In a 71-week trial of 307 adults, oral semaglutide 25 mg daily produced -13.6% versus -2.2% with placebo at week 64 [13].

SELECT tested cardiovascular outcomes in 17,604 adults aged 45 and older with established cardiovascular disease and a BMI of 27 or higher but no diabetes. Over a mean follow-up of 39.8 months, cardiovascular death, nonfatal heart attack or nonfatal stroke occurred in 6.5% on semaglutide 2.4 mg versus 8.0% on placebo (hazard ratio 0.80, 95% CI 0.72 to 0.90), with mean weight change of -9.4% versus -0.9% at week 104 [14].

Semaglutide vs tirzepatide

Tirzepatide (Mounjaro for type 2 diabetes, Zepbound for weight) is labeled as a GIP and GLP-1 receptor agonist, a dual agonist rather than a pure GLP-1 agonist [15].

The direct comparison is SURMOUNT-5, an open-label trial of 751 adults with obesity and no diabetes who received the maximum tolerated dose of tirzepatide (10 or 15 mg) or semaglutide (1.7 or 2.4 mg) for 72 weeks. Mean weight change was -20.2% with tirzepatide and -13.7% with semaglutide, and waist circumference fell 18.4 cm versus 13.0 cm [5]. That trial compared tirzepatide with semaglutide 2.4 mg, not with the 7.2 mg dose [5].

In type 2 diabetes, SURPASS-2 randomized 1,879 adults to tirzepatide 5, 10 or 15 mg or semaglutide 1 mg for 40 weeks. HbA1c fell 2.01, 2.24 and 2.30 points on the three tirzepatide doses versus 1.86 points on semaglutide 1 mg, and weight reductions were 1.9, 3.6 and 5.5 kg greater with tirzepatide [16]. Whether the added GIP receptor activity explains the difference is not established by these trials [15].

One label difference: the tirzepatide label advises a non-oral contraceptive method or an added barrier method for 4 weeks after starting and after each dose increase, while semaglutide labels carry no such advice, and a semaglutide tablet interaction study found no clinically significant change in ethinyl estradiol or levonorgestrel exposure [15][3].

Semaglutide vs liraglutide and dulaglutide

Liraglutide (Saxenda) is a once-daily injection approved for weight management. In the 56-week study described in its label, 3,731 adults with obesity or overweight and a comorbidity lost 7.4% of body weight versus 3.0% on placebo [17]. Semaglutide is injected once weekly [3].

Dulaglutide (Trulicity) is a once-weekly injection for type 2 diabetes in adults and children 10 and older and for cardiovascular risk reduction in adults with type 2 diabetes who have established cardiovascular disease or multiple risk factors; it has no weight-loss indication [18]. In SUSTAIN 7, 1,201 adults with type 2 diabetes on metformin received semaglutide 0.5 or 1 mg or dulaglutide 0.75 or 1.5 mg for 40 weeks. HbA1c fell 1.5 and 1.8 points with semaglutide versus 1.1 and 1.4 points with dulaglutide, and weight fell 4.6 and 6.5 kg versus 2.3 and 3.0 kg [19].

Side effects

Gastrointestinal effects are the common ones, and they are worst during dose escalation [3]. In the pooled Wegovy 2.4 mg injection trials (2,116 adults on Wegovy, 1,261 on placebo, up to 68 weeks), nausea occurred in 44% versus 16%, diarrhea in 30% versus 16%, vomiting in 24% versus 6%, constipation in 24% versus 11%, abdominal pain in 20% versus 10%, headache in 14% versus 10%, fatigue in 11% versus 5%, and hair loss in 3% versus 1% [3]. Any gastrointestinal reaction occurred in 73% versus 47%, and 6.8% versus 3.2% stopped treatment because of an adverse reaction [3].

At 7.2 mg the rates differ: nausea 39%, vomiting 22%, and dysesthesia (altered skin sensation such as burning or pain from touch) 22%, versus 6% for dysesthesia at 2.4 mg and 0% on placebo [3]. In type 2 diabetes trials, nausea occurred in 15.8% on Ozempic 0.5 mg and 20.3% on 1 mg versus 6.1% on placebo [1], and in 11% on Rybelsus 7 mg and 20% on 14 mg versus 6% on placebo [2].

Warnings, contraindications and interactions

Current Wegovy, Ozempic, and Rybelsus/Ozempic tablet labels carry boxed warnings about thyroid C-cell tumors. The labels state that semaglutide caused these tumors in rodents at clinically relevant exposures, while its effect on thyroid C-cell tumors, including medullary thyroid carcinoma, in humans is unknown [3][1][2]. Wegovy, Ozempic, Rybelsus, and Ozempic tablets are contraindicated in people with a personal or family history of medullary thyroid carcinoma or MEN 2, or a prior serious hypersensitivity reaction to semaglutide or an excipient [3][1][2].

Other labeled warnings include acute pancreatitis, acute gallbladder disease, hypoglycemia when combined with insulin or a sulfonylurea, acute kidney injury from volume depletion, severe gastrointestinal reactions, hypersensitivity reactions, diabetic retinopathy complications, heart rate increase and pulmonary aspiration during general anesthesia or deep sedation [3][1]. In adult weight-management trials, cholelithiasis occurred in 1.6% versus 0.7% on placebo and cholecystitis in 0.6% versus 0.2% [3]. In a 2-year trial in type 2 diabetes with high cardiovascular risk, retinopathy complications occurred in 3% versus 1.8% [1]. Mean resting heart rate rose 1 to 4 bpm on Wegovy [3].

The labels say semaglutide is not recommended in patients with severe gastroparesis; they do not state that semaglutide causes gastroparesis [3]. Semaglutide delays gastric emptying and can change absorption of oral medicines; with semaglutide tablets, levothyroxine exposure rose 33% [3].

For pregnancy, the Wegovy label says weight loss offers no benefit in pregnancy and may cause fetal harm, and says to stop Wegovy when pregnancy is recognized and at least 2 months before a planned pregnancy [3]. The suicidal behavior and ideation warning was removed from the Wegovy label in February 2026 after FDA found no increased risk [3][20]. The European Medicines Agency concluded in June 2025 that NAION is a very rare side effect of semaglutide medicines, affecting up to 1 in 10,000 people and corresponding to about one extra case per 10,000 person-years [21].

What happens when semaglutide is stopped

Weight regain is the consistent finding. In STEP 4, 803 adults who had lost a mean 10.6% over a 20-week run-in were randomized to continue semaglutide 2.4 mg or switch to placebo for 48 weeks; weight changed -7.9% on continued treatment versus +6.9% on placebo [22]. In the STEP 1 off-treatment extension, 327 participants regained 11.6 percentage points in the year after stopping, leaving a net loss of 5.6% from baseline versus 0.1% for placebo [23].

Compounded semaglutide

Compounded semaglutide is not FDA approved and is not reviewed by FDA for safety, effectiveness, or quality before marketing [25]. FDA had received 990 adverse event reports for compounded semaglutide as of 2026-05-31, including dosing errors, and states that semaglutide sodium and semaglutide acetate salts are different active ingredients from the approved drug [25]. On 2026-04-30 FDA proposed to exclude semaglutide from the list of bulk substances outsourcing facilities may compound with, with comments due 2026-06-29 and no final decision made [26].