Immediate Versus Criterion-triggered Semaglutide for Suboptimal Clinical Response One Year After Primary Metabolic and Bariatric Surgery
Immediate Versus Criterion-triggered Semaglutide for Suboptimal Clinical Response One Year After Primary Metabolic and Bariatric Surgery: a Randomized, Double-blind Strategy Trial
Roughly one patient in five never reaches the expected weight loss after MBS, and long-term regain after SG is well documented. These patients are identifiable at the 12-month visit. Today they are watched, coached, and treated only when failure is established.
Whether the drug works in this group is no longer the question. BARI-STEP, published this year, randomized 70 patients with less than 20% weight loss after gastric bypass (including one-anastomosis) or sleeve gastrectomy, a mean of seven years after surgery, to semaglutide 2.4 mg or placebo: 18.0% loss versus 0.4% gain at 68 weeks, an adjusted difference of 19.1 percentage points. Its population was mixed, 55.7% with recurrent weight gain and 44.3% with suboptimal initial response, and its exploratory comparison found no difference in drug response between the two presentations. BARI-OPTIMISE showed the same direction with liraglutide, as did a randomized trial after gastric banding. Efficacy is settled.
Timing is not. BARI-STEP recruited patients a mean of seven years past surgery, after failure had hardened. No trial has tested treating at first recognition, the 12-month visit, against the current standard of structured waiting. The field's own reviews name timing and duration as the open questions. The 2024 IFSO international consensus reached 100% agreement that medication after MBS should generally be withheld until the weight plateau, and 100% agreement that adding it for a suboptimal response can then improve outcomes. That is exactly our immediate arm: treat at the plateau, at first recognition. The triggered arm is what clinics actually do: wait for established failure. Both positions rest on expert agreement, not on a trial. This is the randomized test of the consensus pathway. A registered open-label pilot starts tirzepatide at 12 or 18 months but is small, unblinded, and not a strategy comparison.
The 2026 consensus draws the line for us, and this protocol respects it. The Delphi panel defined surgical nonresponse as less than 10% TWL at 12 months, defined recurrent weight gain as regain of more than 25% of lost weight from nadir, and treated a 10% swing in %EWL from nadir as normal physiologic fluctuation. It gave no 12-month label at all to the patient with 10 to 19.9% TWL, and the IFSO Delphi consensus expects the weight nadir up to 2 years after surgery (Obes Surg 2023). So a patient at 14% TWL at one year may still be on the way down, and calling that failure would be wrong. The protocol therefore splits eligibility into two tiers. Below 10% TWL at 12 months: consensus-defined nonresponse, randomized at once, waiting adds nothing. 10 to below 20% TWL: randomized only after a documented plateau, defined in Section 4, with a hard cap at month 18 so waiting cannot drift into neglect. Randomization is stratified by tier, and results are reported by tier.
調査の概要
詳細な説明
Both strategies have a real case, which is what makes this a trial and not a formality. For waiting: some patients improve in the second year without any drug, the drug is expensive, and a treat-everyone-at-12-months policy is unaffordable for most health systems, certainly ours. For immediate treatment: the BARI-STEP effect size, the metabolic cost of two lost years, and the risk that established regain is harder to reverse. Genuine equipoise, between strategies rather than between drug and nothing.
The design removes the ethical problem. Nobody is denied treatment. The triggered arm receives identical lifestyle support and blinded placebo, with guaranteed open-label semaglutide the moment the Delphi recurrence criteria are met, and unconditionally 12 months after randomization if response is still suboptimal. The question the trial asks is when, never whether.
The answer also bears on the operating room. Suboptimal responders are tomorrow's conversion candidates, and conversion carries higher morbidity for around 20% additional weight loss, which is why the field is already comparing drugs against conversion retrospectively. If early drug therapy keeps patients off the revision list, that is measured here as a secondary endpoint.
The health-economic answer may matter most. The triggered strategy tells us what fraction of suboptimal responders never need the drug at all, and what a targeted policy costs per percentage point of weight loss against a treat-all policy. For Egypt and every resource-limited system, that number decides what clinics will actually do. It fits the direction of the 2024 IFSO position on combining medication with surgery while telling payers when to start paying.
研究の種類
入学 (推定)
段階
- フェーズ 4
連絡先と場所
研究連絡先
- 名前：Mohamed Hany Ashour, Professor, MD
- 電話番号：+201002600970
- メール：mohamed.ashour@alexu.edu.eg
研究場所
-
-
-
Alexandria、エジプト、21531
- The surgical department of Medical Research Institute Hospital, Alexandria University
-
コンタクト：
- Mohamed Hany Ashour, Professor, MD
- 電話番号：+201002600970
- メール：mohamed.ashour@alexu.edu.eg
-
コンタクト：
- Mohamed Hany Ashour, Professor, MD
- メール：mohamed.ashour@alexu.edu.eg
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- Primary laparoscopic SG or RYGB at our unit or a participating unit
- %TWL less than 20% from the day of surgery, in one of two tiers. Tier A, surgical nonresponse: below 10% TWL at the 12-month visit; eligible immediately, randomization between months 12 and 14. Tier B, suboptimal response: 10 to below 20% TWL at the 12-month visit; eligible only after a documented plateau, randomization between months 12 and 18 (Plateau, defined. Two clinic weights at least 12 weeks apart differing by less than 2% of body weight, on the trial scale, with no change in treatment between them. This sits inside the swing the consensus panel itself called normal physiologic fluctuation. A Tier B patient still losing at month 12 is re-weighed at months 15 and 18. Reaching 20% TWL at any point means a good response and no enrollment. Still below 20% at month 18 means eligible regardless of plateau; the cap stops watchful waiting from becoming neglect.)
- Anatomy assessed as normal in all: upper endoscopy for every patient, contrast study when symptoms suggest it
- Able to self-inject and consent.
Exclusion Criteria:
- Any GLP-1-based therapy since surgery
- Recurrent weight gain by the consensus definition, regain of more than 25% of the weight lost from nadir; these patients belong to RESURGE, not here
- Anatomical abnormality explaining the poor response (these patients go to the revision pathway, not this trial)
- Pregnancy or conception planned within the study (obesity pharmacotherapy is stopped at least 2 months before any planned conception, per current labeling and the 2026 Standards)
- type 1 diabetes
- medullary thyroid carcinoma or MEN2 history
- pancreatitis history
- untreated severe depression or active eating disorder on psychological review
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
アクティブコンパレータ：Immediate
semaglutide 0.25, 0.5, 1.0, 1.7, 2.4 mg weekly in 4-weekly steps, then 2.4 mg or maximal tolerated dose, with reductions for tolerability permitted and recorded, to 12 months after randomization; in BARI-STEP six patients held reduced doses and the effect stood. |
semaglutide escalated to 2.4 mg weekly, continued for 12 months. |
|
プラセボコンパレーター：Triggered
matched placebo on the identical schedule. Trigger 1: recurrent weight gain by the consensus definition, regain of more than 25% of the weight lost from nadir, confirmed on a second weight 4 weeks later, then immediate open-label semaglutide. Trigger 2: %TWL still below 20% at 12 months after randomization, then open-label semaglutide for the following 12 months. |
Criterion-triggered strategy: matched placebo with identical lifestyle support; guaranteed open-label semaglutide the moment consensus recurrence criteria are met, and in any case 12 months after randomization if response remains suboptimal. |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Percentage total weight loss
時間枠：at 12 months
|
Measured in kilograms from pre-surgery weight at 12 months after randomization, same calibrated scale, morning, light clothing. |
at 12 months
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Percentage total weight loss
時間枠：6, 24 months
|
Measured in kilograms at 6 and 24 months after randomization |
6, 24 months
|
|
change in HbA1c
時間枠：12, 24 months
|
An HbA1c level reflects your average blood sugar over the past two to three months, and any meaningful change typically takes at least 6 weeks to show because red blood cells live for about 3 months. Normal: Below 5.7% Prediabetes: 5.7% to 6.4% Diabetes: 6.5% or higher |
12, 24 months
|
|
systolic and diastolic blood pressure
時間枠：12, 24 months
|
Normal blood pressure is less than 120 mm Hg systolic and less than 80 mm Hg diastolic. Systolic (Top Number): Measures the pressure in your arteries when your heart beats and contracts. Diastolic (Bottom Number): Measures the pressure in your arteries when your heart rests between beats. • Normal: Less than 120 mm Hg systolic and less than 80 mm Hg diastolic. • Elevated: 120-129 mm Hg systolic and less than 80 mm Hg diastolic. • Stage 1 Hypertension (High Blood Pressure): 130-139 mm Hg systolic or 80-89 mm Hg diastolic. • Stage 2 Hypertension: 140 mm Hg or higher systolic, or 90 mm Hg or higher diastolic. • Hypertensive Crisis: Higher than 180 mm Hg systolic and/or higher than 120 mm Hg diastolic. This requires immediate emergency medical care |
12, 24 months
|
|
total cholesterol, LDL, HDL, and triglycerides
時間枠：12, 24 months
|
Normal adult values for a lipid panel are measured in milligrams per deciliter (mg/dL): • Total Cholesterol: Below 200 mg/dL is desirable. (Borderline high is 200-239 mg/dL, and high is 240 mg/dL and above.) • LDL ("Bad") Cholesterol: Below 100 mg/dL is optimal. (130-159 mg/dL is borderline high, and 160-189 mg/dL or higher is high.) • HDL ("Good") Cholesterol: 60 mg/dL and higher is protective. Levels below 40 mg/dL for men or below 50 mg/dL for women are considered low. • Triglycerides: Below 150 mg/dL is normal. (Borderline high is 150-199 mg/dL, and high is 200-499 mg/dL.) |
12, 24 months
|
|
Hand-grip strength
時間枠：0, 12, 24 months
|
A hand grip strength test measures the maximum force of your hand and forearm muscles using a portable device called a handgrip dynamometer. Position yourself: Sit up straight with your feet flat on the floor. Place your arm by your side with your elbow bent at a 90-degree angle and your wrist in a neutral position. Hold the device: Adjust the handle so it fits comfortably in your hand. Squeeze hard: Squeeze the handles as hard as you can for about 3 to 5 seconds without moving your arm or resting the device against your body. Repeat trials: Take three measurements for each hand, resting for 15 to 30 seconds between attempts. Use either the highest score or the average of the trials. A normal hand grip strength score typically ranges from 40 to 56 kg (88 to 123 lbs) for adult men and 25 to 36 kg (55 to 79 lbs) for adult women aged 20-29. |
0, 12, 24 months
|
|
change in IWQOL-Lite-CT total and domain scores
時間枠：0, 12, 24 months
|
The IWQOL-Lite-CT (Impact of Weight on Quality of Life-Lite Clinical Trials Version) score ranges from 0 to 100, where 100 represents the best possible quality of life and functioning (meaning zero weight-related impairment). • Total Score Range: 0-100 (higher = better quality of life) • Domain/Composite Scores: 0-100 • Raw scores are converted or transformed to a 0-100 scale for standard reporting. |
0, 12, 24 months
|
協力者と研究者
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
その他の研究ID番号
- TOP-UP Trial
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD 共有サポート情報タイプ
- STUDY_PROTOCOL
- SAP
- ICF
- ANALYTIC_CODE
- CSR
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