Gastrointestinal adverse events associated with semaglutide: A pharmacovigilance study based on FDA adverse event reporting system

Probably not a substantial claim: may not pass S3 (load-bearing).

1,005 patients reported weight data, with a median weight of 96.16 kg.

“1,005 patients reported weight data, with the median weight of 96.16 kg.”

• AssumptionRests on an assumption: FAERS reports are sufficiently accurate and complete to detect and quantify semaglutide-associated gastrointestinal adverse events.

May combine two claims.

Since there were only 2 patients younger than 18 years old, they did not show significant signal strength with ROR025 0.54.

“Since there were only 2 patients younger than 18 years old, they did not show significant signal strength with ROR025 0.54.”

• AssumptionRests on an assumption: FAERS reports are sufficiently accurate and complete to detect and quantify semaglutide-associated gastrointestinal adverse events.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The report proportions of body weight >100, 80-100, and <80 kg were 42.39%, 34.43%, and 23.18%, respectively.

“The report proportions of body weight >100, 80–100, and <80 kg were 42.39, 34.43, and 23.18%, respectively.”

• AssumptionRests on an assumption: FAERS reports are sufficiently accurate and complete to detect and quantify semaglutide-associated gastrointestinal adverse events.

May combine two claims.

11 out of the 45 adverse events (24.44%) showing statistically significant disproportionality were categorized as important medical events, and only 2 (4.44%) as designated medical events, including pancreatitis and pancreatitis acute.

“Overall, 11 out of the 45 AEs (24.44%) showing statistically significant disproportionality were categorized as IMEs, and only 2 (4.44%) as DMEs, including pancreatitis and pancreatitis acute (Table 3).”

• AssumptionRests on an assumption: FAERS reports are sufficiently accurate and complete to detect and quantify semaglutide-associated gastrointestinal adverse events.

May combine two claims.

Based on the clinical priority assessment results, 1 (2.22%), 22 (48.89%), and 22 (48.89%) adverse events were identified as strong, moderate, and weak clinical priority, respectively.

“Based on the clinical priority assessment results, 1 (2.22%), 22 (48.89%), and 22 (48.89%) AEs were identified as strong, moderate and weak clinical priority, respectively.”

• Also stated in: § Results · plain

  “One strong, 22 moderate and 22 weak clinical priority signals were defined.”

• AssumptionRests on an assumption: FAERS reports are sufficiently accurate and complete to detect and quantify semaglutide-associated gastrointestinal adverse events.

May combine two claims.

Serious outcomes of gastrointestinal and overall adverse event reports were recorded in 1,778 and 3,601 cases, including 40 (2.25%) and 102 (2.83%) deaths, respectively.

“Serious outcomes of gastrointestinal and overall AEs reports were recorded in 1,778 and 3,601 cases, including 40 (2.25%) and 102 (2.83%) deaths, respectively.”

• AssumptionRests on an assumption: FAERS reports are sufficiently accurate and complete to detect and quantify semaglutide-associated gastrointestinal adverse events.

May combine two claims.

The 45 semaglutide-related gastrointestinal adverse events showed statistically significant signal strengths compared to non-semaglutide-associated gastrointestinal adverse events, with ROR025 values ranging from 1.01 (hypoaesthesia oral) to 42.03 (eructation).

“The 45 semaglutide-related gastrointestinal AEs also showed statistically significant signal strengths as compared to non-semaglutide-associated gastrointestinal AEs, with values of signals ranging from a ROR025 of 1.01 (hypoaesthesia oral) to 42.03 (eructation).”

• Also stated in: § Results · plain

  “We identified 5,442 cases of semaglutide-associated gastrointestinal AEs, with 45 signals detected, ranging from a ROR025 of 1.01 (hypoaesthesia oral) to 42.03 (eructation), among which 17 AEs were identified as new and unexpected signals.”

• AssumptionRests on an assumption: FAERS reports are sufficiently accurate and complete to detect and quantify semaglutide-associated gastrointestinal adverse events.
• AssumptionRests on an assumption: Reports in which semaglutide is recorded as the primary suspected drug are actually caused by semaglutide.

May combine two claims.

Other serious events and hospitalizations were the most frequently reported serious outcomes of semaglutide treatment, occurring in 1,103 (62.04%) and 772 (43.42%) gastrointestinal adverse events and 2,311 (64.18%) and 1,430 (39.71%) overall adverse events, respectively.

“Other serious events and hospitalizations were the most frequently reported serious outcomes of semaglutide treatment, occurring in 1,103 (62.04%), 772 (43.42%) gastrointestinal AEs and 2,311 (64.18%), 1,430 (39.71%) overall AEs, respectively.”

• AssumptionRests on an assumption: FAERS reports are sufficiently accurate and complete to detect and quantify semaglutide-associated gastrointestinal adverse events.

May combine two claims.

After the SOC of gastrointestinal disorders was assessed separately by sex, age, body weight, and reporter type, the lower limits of ROR values were >1 in all stratified subgroups, revealing that there was still a strong statistical correlation between semaglutide and gastrointestinal disorders.

“As shown in Figure 3, after SOC of gastrointestinal disorders was assessed separately by sex, age, body weight and reporters' type, the lower limits of ROR values were >1 in all stratified subgroups, revealing that there was still a strong statistical correlation between semaglutide and gastrointestinal disorders.”

• Also stated in: § Results · plain

  “Notably, the association between semaglutide and gastrointestinal disorders remained when stratified by age, body weight, sex and reporter type.”

• AssumptionRests on an assumption: FAERS reports are sufficiently accurate and complete to detect and quantify semaglutide-associated gastrointestinal adverse events.
• AssumptionRests on an assumption: Reports in which semaglutide is recorded as the primary suspected drug are actually caused by semaglutide.

Probably not a substantial claim: may not pass S3 (load-bearing).

40.25% of gastrointestinal reports were submitted by healthcare professionals (n = 2,183), compared to 59.75% reported by consumers (n = 3,240).

“Additionally, 40.25% of the gastrointestinal reports were submitted by healthcare professionals (n = 2,183), compared to 59.75% reported by consumers (n = 3,240).”

• AssumptionRests on an assumption: FAERS reports are sufficiently accurate and complete to detect and quantify semaglutide-associated gastrointestinal adverse events.

May combine two claims.

Reports of semaglutide-related gastrointestinal adverse events increased from 2018 to 2021, with 1,847 reports in 2021, almost four times the 454 reports in 2018.

“gastrointestinal AEs reported a remarkable increase from 2018 to 2021, with the annual reports in 2021 (n = 1,847) almost 4 times of 2018 (n = 454).”

May combine two claims.

T2DM was the most reported indication (n = 1,656, 59.83%), followed by other unspecified diabetes mellitus (n = 715, 25.83%) and obesity (n = 133, 4.80%).

“T2DM was the most reported indication (n = 1,656, 59.83%), followed by other unspecified diabetes mellitus (n = 715, 25.83%) and obesity (n = 133, 4.80%).”

• AssumptionRests on an assumption: FAERS reports are sufficiently accurate and complete to detect and quantify semaglutide-associated gastrointestinal adverse events.

May combine two claims.

Patient age (p < 0.001) and body weight (p = 0.006), but not sex (p = 0.251), might be associated with an increased risk of gastrointestinal adverse event severity.

“Patient age (p < 0.001) and body weight (p = 0.006) rather than sex (p = 0.251) might be associated with an increased risk of gastrointestinal AEs severity.”

• Also stated in: § Conclusion · hedged

  “Patient age (p < 0.001) and body weight (p = 0.006) rather than sex (p = 0.251) might be associated with an increased risk of gastrointestinal AEs severity.”

May combine two claims.

Pancreatitis (n = 389, ROR025 = 18.29) was classified as strong clinical priority with the highest priority score of 8.

“Pancreatitis (n = 389, ROR025 = 18.29) was classified as strong clinical priority with the highest priority score 8.”

• AssumptionRests on an assumption: FAERS reports are sufficiently accurate and complete to detect and quantify semaglutide-associated gastrointestinal adverse events.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Gender data were available for 5,312 patients, and females accounted for a larger proportion than males (3,064 vs. 2,248).

“Gender data were available for 5,312 patients, and females accounted for a larger proportion than males (3,064 vs. 2,248).”

• AssumptionRests on an assumption: FAERS reports are sufficiently accurate and complete to detect and quantify semaglutide-associated gastrointestinal adverse events.

May combine two claims.

There were statistically significant differences in age (61 vs. 64.5 years; p < 0.001) and body weight (95 vs. 98.1 kg; p = 0.006) between severe and non-severe cases of gastrointestinal adverse event patients receiving semaglutide.

“As shown in Table 2, there were statistically significant differences in age (61 vs. 64.5 years; p < 0.001) and body weight (95 vs. 98.1 kg; p = 0.006) between severe and non-severe cases of gastrointestinal AEs patients receiving semaglutide.”

• AssumptionRests on an assumption: FAERS reports are sufficiently accurate and complete to detect and quantify semaglutide-associated gastrointestinal adverse events.

May combine two claims.

The most frequently reported gastrointestinal adverse events were nausea (n = 2,369), vomiting (n = 1,338), diarrhea (n = 1,195), constipation (n = 663), abdominal pain upper (n = 490), abdominal pain (n = 398), and pancreatitis (n = 389).

“The most frequently reported gastrointestinal AEs were nausea (n = 2,369), vomiting (n = 1,338), diarrhea (n = 1,195), constipation (n = 663), abdominal pain upper (n = 490), abdominal pain (n = 398), and pancreatitis (n = 389).”

• AssumptionRests on an assumption: FAERS reports are sufficiently accurate and complete to detect and quantify semaglutide-associated gastrointestinal adverse events.

May combine two claims.

All adverse event outcomes for pancreatic carcinoma metastatic (n = 12) were severe, while all oropharyngeal discomfort (n = 11) were non-severe.

“Of note, all AEs outcomes for pancreatic carcinoma metastatic (n = 12) were severe, while all oropharyngeal discomfort (n = 11) were non-severe.”

• AssumptionRests on an assumption: FAERS reports are sufficiently accurate and complete to detect and quantify semaglutide-associated gastrointestinal adverse events.

May combine two claims.

The proportion of serious adverse events was similar in males and females (33.81% vs. 32.31%), with no statistical difference (p = 0.251).

“the proportion of serious AEs was similar in males and females (33.81 vs. 32.31%), and there was no statistical difference between the two groups (p = 0.251).”

May combine two claims.

In a stratified analysis, the association with gastrointestinal adverse events was stronger in subgroups >65 years than in subgroups 18-65 years, with a higher ROR025 of 4.19.

“our further stratified analysis showed a stronger association with gastrointestinal AEs in subgroups >65 years than in subgroups 18–65 years with a higher ROR025 of 4.19.”

May combine two claims.

ROR025 values of the subgroups <80 kg and 80-100 kg were similar (3.49 and 3.85, respectively), but both showed positive significant disproportionation signals.

“ROR025 values of the two subgroups smaller than 80 and 80–100 kg were similar (3.49 and 3.85, respectively), but both showed positive significant disproportionation signals (Figure 3).”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

There were 22 moderate and 22 weak clinical priority signals.

“In addition, 22 moderate and 22 weak clinical priority signals were defined.”

May combine two claims.

Among the 45 gastrointestinal adverse events, 17 new and unexpected adverse events, including dry mouth, hypophagia, gastrointestinal sounds abnormal, bowel movement irregularity, feces discolored, and pancreatic carcinoma metastatic, were detected and were not reported in the drug label.

“Among the 45 gastrointestinal AEs, 17 new and unexpected AEs, including dry mouth, hypophagia, gastrointestinal sounds abnormal, bowel movement irregularity, feces discolored, pancreatic carcinoma metastatic, etc, were detected in our pharmacovigilance study, which were not reported in the drug label.”

• AssumptionRests on an assumption: The drug label is a complete and accurate list of known adverse events for semaglutide, so adverse events not listed in the label are new and unexpected.

May combine two claims.

Among the moderate clinical priority signals, the most commonly reported semaglutide-related adverse events were nausea (score 6), vomiting (score 6), diarrhea (score 5), constipation (score 6), and abdominal pain (score 5).

“among the moderate clinical priority signals, the most commonly reported semaglutide-related AEs were nausea (score 6), vomiting (score 6), diarrhea (score 5), constipation (score 6), and abdominal pain (score 5)”

May combine two claims.

The subgroup with body weight >100 kg had the highest ROR025 value of 5.06, presenting the strongest signal strength.

“the subgroup with body weight >100 kg had the highest ROR025 value of 5.06, presenting the strongest signal strength.”

May combine two claims.

The association between semaglutide and gastrointestinal adverse events was stronger in males than in females, with a higher ROR025 value (4.33 vs. 3.65).

“The association was stronger in males than in females with a higher ROR025 value (4.33 vs. 3.65).”

May combine two claims.

A total of 389 cases of semaglutide-associated pancreatitis were extracted from the FAERS database, with 333 reported as serious.

“A total of 389, 61, 49, 16, and 12 cases of semaglutide-associated pancreatitis, pancreatitis acute, pancreatic carcinoma, obstructive pancreatitis and pancreatic carcinoma metastatic were extracted from the FAERS database, with 333, 54, 46, 15, and 12 reported as serious cases, respectively (Table 2).”

May combine two claims.

Severe outcomes were detected in 46 cases of pancreatic carcinoma and all 12 cases of pancreatic carcinoma metastatic, including 7 and 3 deaths, respectively.

“we detected severe outcomes in 46 cases of pancreatic carcinoma and all cases of pancreatic carcinoma metastatic (n = 12), including 7 and 3 deaths, respectively”

May combine two claims.

In the time-to-onset analysis, the median time-to-onset for pancreatitis was 23 days, while for moderate and weak clinical priority signals it was 6 and 7 days, respectively.

“In the TTO analysis, the median TTO for pancreatitis was 23 days, while for moderate and weak clinical priority signals, they were 6 and 7 days, respectively.”

May combine two claims.

Pancreatitis acute (score 7), obstructive pancreatitis (score 5), and pancreatic carcinoma metastatic (score 5) were moderate clinical priority signals.

“Pancreatitis acute (score 7), obstructive pancreatitis (score 5) and pancreatic carcinoma metastatic (score 5) were considered to be moderate clinical priority signals.”

May combine two claims.

Pancreatitis ranked 7th among the top 10 gastrointestinal adverse events in terms of number of reports, with a strong signal strength (ROR 20.27, 95% CI 18.29-22.47).

“pancreatitis ranked 7th among the top 10 gastrointestinal AEs in terms of the number of reports, showing strong signal strength with ROR 20.27 (18.29–22.47) in the current study (Figure 2).”

Classified as probably not a substantial claim.

All gastrointestinal adverse events with at least ten reports were selected to reduce the likelihood of false positives.

“All gastrointestinal AEs with at least ten reports were selected to reduce the likelihood of false positives.”

Classified as probably not a substantial claim.

Deduplication was performed before statistical analysis.

“All data were imported into MySQL software (v8.0; Oracle, Sweden), and the deduplication process was performed before statistical analysis.”

Classified as probably not a substantial claim.

The previous study demonstrated that semaglutide had a higher pooled reporting odds ratio and later pooled time-to-onset median of gastrointestinal adverse events compared with liraglutide.

“This study demonstrated that semaglutide had a higher pooled ROR and later pooled time-to-onset median of gastrointestinal AEs compared with those of liraglutide.”

• cites [13] Zhou, 2022, Difference in gastrointestinal risk associated with use of GLP-1 receptor agonists: a real-world pharmacovigilance study, Diabetes Metabol Syndrome Obesity Targets Therapy. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

The SUSTAIN-6 clinical trial showed a statistically significant reduction in the risk of cardiovascular events in the semaglutide group compared with the placebo group (6.6 vs. 8.9%, hazard ratio 0.74; 95% CI 0.58-0.95; p < 0.001).

“the SUSTAIN-6 clinical trial that showed a statistically significant reduction in the risk of cardiovascular events in the semaglutide group compared with placebo group (6.6 vs. 8.9%, hazard ratio, 0.74; 95% confidence interval [CI], 0.58–0.95; p < 0.001) (4, 5).”

• cites [4] Marso, 2016, Semaglutide and cardiovascular outcomes in patients with type 2 diabetes, N Engl J Med. sourceNot checked yet

  Not checked in the free run.

• cites [5] WashingtonNot checked yet

  Not checked in the free run.

May combine two claims.

Reports of semaglutide-related gastrointestinal adverse events will continue to increase in 2022, based on 949 cases in the first quarter of 2022 alone, far above the average quarterly number for 2018-2021.

“Based on our data prediction, reports of semaglutide will continue to increase in 2022, as there are 949 cases in the first quarter of 2022 alone, which is far above the average quarterly number for 2018–2021.”

May combine two claims.

All of the disproportionality signals had early failure type features, suggesting that the risk of gastrointestinal adverse event occurrence gradually decreased over time.

“All of the disproportionality signals had early failure type features, suggesting that the risk of gastrointestinal AEs occurrence gradually decreased over time.”

• AssumptionRests on an assumption: FAERS reports are sufficiently accurate and complete to detect and quantify semaglutide-associated gastrointestinal adverse events.

May combine two claims.

In a pooled analysis of the STEP 1-3 clinical trials, most gastrointestinal adverse events reported with semaglutide were non-serious (99.5%) and mild-to-moderate (98.1%) in severity, and did not necessitate dose reduction or discontinuation.

“A pooled analysis of the STEP 1–3 clinical trials of evaluating the gastrointestinal AE profile of semaglutide revealed that most gastrointestinal AEs reported were non-serious (99.5% of AEs) and mild-to-moderate (98.1%) in severity, which did not necessitate dose reduction or discontinuation (26).”

• cites [26] Wharton, 2022, Gastrointestinal tolerability of once-weekly semaglutide 24 mg in adults with overweight or obesity, and the relationship between gastrointestinal adverse events and weight loss, Diabetes Obesity Metabol. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Semaglutide was approved by the US FDA in December 2017 for the treatment of type 2 diabetes mellitus in adults.

“Semaglutide, a novel GLP-1RA with an extended half-life of ~1 week, was approved by the US Food and Drug Administration (FDA) in December 2017 for the treatment of T2DM in adult (3).”

• cites [3] WashingtonNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S4 (based).

Real-world data regarding semaglutide's long-term gastrointestinal safety and tolerability in a large sample population are incomplete.

“However, real-world data regarding its long-term gastrointestinal safety and tolerability in large sample population are incomplete.”

Classified as probably not a substantial claim.

Reports were manually checked to select the highest primary ID when the case ID was the same.

“We further checked the reports manually to select the highest primary ID, when the case ID was the same.”

Classified as probably not a substantial claim.

Reports with input errors (EVENT_DT earlier than START_DT), inaccurate date entries, and missing specific data were excluded.

“In order to ensure the accuracy of this calculation, reports with input errors (EVENT_DT earlier than START_DT), inaccurate date entries and missing specific data were excluded.”

Probably not a substantial claim: may not pass S3 (load-bearing).

In January 2020, the FDA expanded the indication of semaglutide to include T2DM adults with cardiovascular disease.

“Subsequently, in January 2020, the FDA expanded the indication of semaglutide to include T2DM adults with cardiovascular disease based primarily on the SUSTAIN-6 clinical trial that showed a statistically significant reduction in the risk of cardiovascular events in the semaglutide group compared with placebo group (6.6 vs. 8.9%, hazard ratio, 0.74; 95% confidence interval [CI], 0.58–0.95; p < 0.”

• cites [4] Marso, 2016, Semaglutide and cardiovascular outcomes in patients with type 2 diabetes, N Engl J Med. sourceNot checked yet

  Not checked in the free run.

• cites [5] WashingtonNot checked yet

  Not checked in the free run.

Classified as probably not a substantial claim.

Stratification analysis was performed by gender, age, weight, and reporter type separately.

“we performed stratification analysis by gender (female and male), age (18 ≤ and ≤ 64, >65 years), weight (<80, 80 ≤ and ≤ 100, >100 kg) and reporters (healthcare professional and consumer) separately.”

Classified as probably not a substantial claim.

The case ID was chosen as the key filter to remove duplicate records.

“The primary ID was the primary link field (primary key) between different data files, and the case ID was chosen as the key filter in our study to remove duplicate records (18).”

• cites [18] Wu, 2022, Acute kidney injury associated with remdesivir: a comprehensive pharmacovigilance analysis of COVID-19 reports in FAERS, Front Pharmacol. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

GLP-1 receptor agonist use may be associated with an increased risk of acute pancreatitis and thyroid cancer.

“In addition, GLP-1RAs use may be associated with an increased risk of acute pancreatitis and thyroid cancer, and the FDA has warned the public about these AEs (10–12).”

• cites [10] Jensen, 2015, Is there a link between liraglutide and pancreatitis? A post hoc review of pooled and patient-level data from completed liraglutide type 2 diabetes clinical trials, Diabetes Care. sourceNot checked yet

  Not checked in the free run.

• cites [11] Faillie, 2014, Pancreatitis associated with the use of GLP-1 analogs and DPP-4 inhibitors: a case/non-case study from the French pharmacovigilance database, Acta Diabetol. sourceNot checked yet

  Not checked in the free run.

• cites [12] Elashoff, 2011, Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1-based therapies, Gastroenterology. sourceNot checked yet

  Not checked in the free run.

Classified as probably not a substantial claim.

The most common adverse events reported with GLP-1 receptor agonists were gastrointestinal disorders, such as nausea, diarrhea, vomiting, and abdominal pain.

“The most common adverse events (AEs) reported with GLP-1RAs were gastrointestinal disorders, such as nausea, diarrhea, vomiting, and abdominal pain, etc (7–9).”

• cites [7] Sun, 2015, Gastrointestinal adverse events of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a systematic review and network meta-analysis, Diabetes Technol Therapeut. sourceNot checked yet

  Not checked in the free run.

• cites [8] Wysham, 2014, Efficacy and safety of dulaglutide added onto pioglitazone and metformin vs. exenatide in type 2 diabetes in a randomized controlled trial (AWARD-1), Diabetes Care. sourceNot checked yet

  Not checked in the free run.

• cites [9] Nauck, 2013, Long-term efficacy and safety comparison of liraglutide, glimepiride and placebo, all in combination with metformin in type 2 diabetes: 2-year results from the LEAD-2 study, Diabetes Obesity Metabol. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Gastrointestinal risks in type 2 diabetes mellitus occurred more often in females (52.32%).

“which was in line with the finding that gastrointestinal risks in T2DM occurred more often in females (52.32%) (13).”

• cites [13] Zhou, 2022, Difference in gastrointestinal risk associated with use of GLP-1 receptor agonists: a real-world pharmacovigilance study, Diabetes Metabol Syndrome Obesity Targets Therapy. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

A safety study of injectable semaglutide for type 2 diabetes suggested that thyroid and pancreatic safety had not been substantiated.

“Safety study of injectable semaglutide for type 2 diabetes suggested that the thyroid and pancreatic safety had not been substantiated (43).”

• cites [43] Peter, 2020, Safety of injectable semaglutide for type 2 diabetes, Exp Opin Drug Saf. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

The study focused only on adverse events in one reaction group, so the relationship between semaglutide and other system organ classes remains unknown.

“we focus only on AEs in one reaction group, and the deep relationship between semaglutide and other system organ classes remains unknown.”

Probably not a substantial claim: may not pass S2 (checkable), S4 (based). May combine two claims.

The possibility of submitting false, underreported, inaccurate, incomplete, and delayed reports to FAERS can hardly be solved, which may result in inevitable bias.

“the possibility of submitting false, underreported, inaccurate, incomplete, and delayed reports can hardly be solved, which may result in inevitable bias.”

Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).

The safety signal spectrum of semaglutide might change over time as more reports are submitted.

“In summary, the safety signal spectrum of semaglutide might change over time as more reports were submitted.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The higher frequency of gastrointestinal adverse events in patients aged 18-65 years might be due to the high incidence of diabetes in this age group.

“which might be due to the high incidence of diabetes in patients aged 18–65 years (27).”

• cites [27] Zhao, 2021, Hypoglycemia following the use of glucagon-like peptide-1 receptor agonists: a real-world analysis of post-marketing surveillance data, Ann Transl Med. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Weight loss with semaglutide ranged from 9.6 to 17.1% in participants without gastrointestinal adverse events and from 11.4 to 17.7% in those with gastrointestinal adverse events, suggesting gastrointestinal adverse events contribute little to the weight-loss benefit of semaglutide.

“Researchers observed that weight loss with semaglutide ranged from 9.6 to 17.1% in participants without gastrointestinal AEs and from 11.4 to 17.7% in those with gastrointestinal AEs, suggesting gastrointestinal AEs appeared to contribute little to the weight-loss benefit of semaglutide”

• cites [26] Wharton, 2022, Gastrointestinal tolerability of once-weekly semaglutide 24 mg in adults with overweight or obesity, and the relationship between gastrointestinal adverse events and weight loss, Diabetes Obesity Metabol. sourceNot checked yet

  Not checked in the free run.

• cites [36] Ahrén, 2018, Semaglutide induces weight loss in subjects with type 2 diabetes regardless of baseline BMI or gastrointestinal adverse events in the SUSTAIN 1 to 5 trials, Diabetes Obesity Metabol. sourceNot checked yet

  Not checked in the free run.

• cites [37] Lingvay, 2020, Superior weight loss with once-weekly semaglutide vs other glucagon-like peptide-1 receptor agonists is independent of gastrointestinal adverse events, BMJ Open Diabetes Res Care. sourceNot checked yet

  Not checked in the free run.

Classified as probably not a substantial claim.

Nreu et al. and Monami et al. found that the incidence of pancreatitis and pancreatic cancer with GLP-1 receptor agonists including semaglutide was not significantly different from that observed in comparator arms.

“Both Nreu et al. (39), Monami et al. (40) found that the incidence of pancreatitis and pancreatic cancer with GLP-1 RAs including semaglutide was not significant from that observed in comparator arms.”

• cites [39] Nreu, 2020, Pancreatitis and pancreatic cancer in patients with type 2 diabetes treated with glucagon-like peptide-1 receptor agonists: an updated meta-analysis of randomized controlled trials, Miner Endocrinol. sourceNot checked yet

  Not checked in the free run.

• cites [40] Monami, 2017, Safety issues with glucagon-like peptide-1 receptor agonists (pancreatitis, pancreatic cancer and cholelithiasis): data from randomized controlled trials, Diabetes Obesity Metabol. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Our post-marketing pharmacovigilance analysis demonstrated a strong association between semaglutide exposure and the occurrence of pancreatitis and pancreatic cancer.

“our post-marketing pharmacovigilance analysis based on big data demonstrated a strong association between semaglutide exposure and the occurrence of pancreatitis and pancreatic cancer, further confirming the results of clinical trials.”

May combine two claims.

In the semaglutide 2.4 mg arm, the median durations of nausea, diarrhea, and vomiting were 8, 3, and 2 days, respectively.

“indicating the median durations of nausea, diarrhea and vomiting were 8, 3, and 2 days respectively, in the semaglutide 2.4 mg arm (26).”

• cites [26] Wharton, 2022, Gastrointestinal tolerability of once-weekly semaglutide 24 mg in adults with overweight or obesity, and the relationship between gastrointestinal adverse events and weight loss, Diabetes Obesity Metabol. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The Weibull parameter can be used to predict the period before an adverse event occurs and provides relevant insights for patient pharmacological management in clinical practice.

“It was reported that Weibull parameter could be used to predict the period before an AE occured and provided relevant insights for patient pharmacological management in clinical practice (22).”

• cites [22] Mazhar, 2021, The impact of anti-TNFα agents on weight-related changes: new insights from a real-world pharmacovigilance study using the FDA adverse event reporting system (FAERS) database, Exp Opin Biol Therapy. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Among patients receiving semaglutide, 86% of those aged ≥65 years reported adverse events compared with 76% of those aged 45-65 years and 80% of those aged <45 years.

“Among patients receiving semaglutide, 86% of those aged ≥65 years reported AEs compared with 76% of those aged 45–65 years and 80% of those aged <45 years (29).”

• cites [29] Rosenstock, 2019, Effect of additional oral semaglutide vs. sitagliptin on glycated hemoglobin in adults with type 2 diabetes uncontrolled with metformin alone or with sulfonylurea: the PIONEER 3 randomized clinical trial, JAMA. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Semaglutide was significantly more effective in weight loss than liraglutide for overweight or obesity without diabetes, and it also exhibited excellent effect in East Asian populations.

“Recent studies have shown that semaglutide was significantly more effective in weight loss than liraglutide for overweight or obesity without diabetes, and it also exhibited excellent effect in East Asian populations (34, 35).”

• cites [34] Rubino, 2022, Effect of weekly subcutaneous semaglutide vs. daily liraglutide on body weight in adults with overweight or obesity without diabetes: the STEP 8 randomized clinical trial, JAMA. sourceNot checked yet

  Not checked in the free run.

• cites [35] Kadowaki, 2022, Semaglutide once a week in adults with overweight or obesity, with or without type 2 diabetes in an east Asian population (STEP 6): a randomised, double-blind, double-dummy, placebo-controlled, phase 3a trial, Lancet Diabetes Endocrinol. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

The FDA approved semaglutide in June 2021 for long-term weight management in overweight or people with obesity.

“the FDA approved semaglutide in June 2021 for long-term weight management in overweight or people with obesity (31–33).”

• cites [31] Wilding, 2021, Once-weekly semaglutide in adults with overweight or obesity, N Engl J Med. sourceNot checked yet

  Not checked in the free run.

• cites [32] Wadden, 2021, Effect of subcutaneous semaglutide vs. placebo as an adjunct to intensive behavioral therapy on body weight in adults with overweight or obesity: the STEP 3 randomized clinical trial, JAMA. sourceNot checked yet

  Not checked in the free run.

• cites [33] Rubino, 2021, Effect of continued weekly subcutaneous semaglutide vs. placebo on weight loss maintenance in adults with overweight or obesity: the STEP 4 randomized clinical trial, JAMA. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Gastrointestinal adverse events associated with GLP-1 receptor agonists are dose dependent and decline over time.

“This result corresponded to a research showing that the gastrointestinal AEs associated with GLP-1RAs were dose dependent and decline over time (45).”

• cites [45] Amori, 2007, Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis, JAMA. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

All of the disproportionality signals had early failure type characteristics, suggesting that the majority of patients developed gastrointestinal adverse events within 1 week or 1 month of semaglutide treatment, and that the risk of gastrointestinal adverse events occurrence gradually decreased over time.

“All of the disproportionality signals had early failure type characteristics, suggesting that the majority of patients developed gastrointestinal AEs within 1 week or 1 month of semaglutide treatment, and that the risk of gastrointestinal AEs occurrence gradually decreased over time.”

• Also stated in: § Conclusion · hedged

  “All of the disproportionality signals had early failure type features, suggesting that the majority of patients developed gastrointestinal AEs within 1 week or 1 month of semaglutide treatment, and that the risk of gastrointestinal AEs occurrence gradually decreased over time.”