#264 Hotcakes: Semaglutide for weight loss, Abx for Diverticulitis, Periop COVID19

March 29, 2021 | By Matthew Watto, MD

Fresh hotcakes! Practice-changing articles that you need to know: semaglutide for weight loss; metronidazole plus a fluoroquinolone versus amoxicillin/clavulanic acid for uncomplicated diverticulitis; and the perioperative risks of COVID19. We’re joined by Dr. Adnan Khan (Chief resident, VCU Internal Medicine Residency) and our fearless leader of critical appraisal, internist/epidemiologist, Rahul Ganatra MD, MPH, @rbganatra (VA Boston).

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Credits

• Written, Produced and hosted by: Rahul Ganatra MD, MPH; Adnan Khan MD; Matthew Watto MD, FACP; Paul Williams MD, FACP   
• Cover Art: Matthew Watto MD, FACP
• Editor: Rahul Ganatra MD (written materials); Clair Morgan of nodderly.com

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Show Segments

• Intro, disclaimer
• Pick of the week: Dark (Netflix TV series)
• Preventive Medicine Updates
• Semaglutide for weight loss
• Amox-clav vs FQ-metronidazole for Diverticulitis
• Perioperative COVID19 infection and timing of surgery
• Rahul’s take-home points
• Outro

Primary Care Updates

1. Colon Cancer Screening Update: Consider screening average-risk adults age 45 to 49 years old (ACG guidelines 2021)
2. Lung cancer screening Update: Screen adults age 50 to 80 years old with at least 20 pack-years smoking who quit less than 15 years ago (USPSTF)

Hotcakes

Wilding JPH et al; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Feb 10. doi: 10.1056/NEJMoa2032183. Epub ahead of print. PMID: 33567185. https://pubmed.ncbi.nlm.nih.gov/33567185/ 

Question:  How safe and effective is once-weekly injected semaglutide (plus weight-loss counseling) for achieving weight loss among overweight or obese adults without diabetes?

Comparison: 1961 Participants were randomized to receive semaglutide 2.4mg once weekly or placebo with lifestyle interventions for 68 weeks. The coprimary endpoints were percentage weight change from baseline to week 68 and reduction of body weight by 5% or more.

Results: The intention-to-treat analysis for the endpoint of mean weight change was -14.85% with semaglutide and -2.4% with placebo, for a difference of -12.44% (P <.001).  Also, 86.4% of participants in the semaglutide group achieved ≥5% bodyweight reduction, vs 31.5% of the placebo group. (p<.001).  Regarding adverse events and drug discontinuation, 9.8% of patients in the semaglutide group and 6.4% in the placebo group reported serious adverse events, with more serious GI disorders (1.4% in semaglutide vs 0% in placebo). 

Bottom Line: This was a positive study. Semaglutide was associated with a large reduction in weight compared with placebo when used as an adjunct to lifestyle interventions. This treatment effect is larger than currently approved weight loss medications.

Hotcakes rating:  Half Stack (B) rating from Adnan

Gaber CE, et al. Comparative Effectiveness and Harms of Antibiotics for Outpatient Diverticulitis: Two Nationwide Cohort Studies. Ann Intern Med. 2021 Feb 23. doi: 10.7326/M20-6315. Epub ahead of print. PMID: 33617725. https://pubmed.ncbi.nlm.nih.gov/33617725/ 

Question: What are the comparative effectiveness and harms of metronidazole plus a fluoroquinolone versus amoxicillin-clavulanate in treating outpatient diverticulitis?

Comparison: This was an active-comparison, new-user (ACNU!), retrospective cohort study comparing the use of metronidazole/fluoroquinolone with amoxicillin-clavulanate for treatment of uncomplicated acute diverticulitis. Outcomes included inpatient admission for diverticulitis, urgent surgery, or Clostridioides difficile infection (CDI) in the year after diagnosis.  The authors also assessed risk for elective surgery within 3 years of diagnosis of diverticulitis.

Results: Metronidazole/fluoroquinolone was used 89% of the time in the MarketScan cohort (median age 52) and 86.7% of the time in the Medicare cohort (median age 73).  In the MarketScan group, there was no difference between treatment groups in 1-year hospital admission risk [risk difference, 0.1%, 95% CI, -0.3-0.6], 1-year urgent surgery risk [risk difference, 0.0%, 95% CI, -0.1 to 0.1], or 3-year elective surgery risk [risk difference, 0.2%, 95% CI -0.3-0.7].  There was also no difference in the 1-year risk of CDI between treatment groups.

Results were similar in the Medicare group, except the risk of CDI was significantly higher for metronidazole/fluoroquinolone (1.2%) compared to the amoxicillin-clavulanate (0.6%), with a difference of 0.6 percentage points [CI 0.2-1.0], and a number needed to treat to harm calculated as 167.

Bottom Line: In two large nationwide cohorts, there was no significant difference in inpatient admissions, urgent surgeries, and elective surgeries between patients treated with metronidazole and a fluoroquinolone versus those treated with amoxicillin-clavulanate.  In the Medicare cohort, treatment with metronidazole/fluoroquinolone was associated with a higher risk of CDI.

Hotcakes rating: Half-stack (B-rating) from Paul.  It has all the limits of chart-mining studies but was incredibly thoughtful, well-designed, and compelling enough to change practice.

Further Reading: 

Black Box Warning on FQ – FDA July 2016

COVIDSurg Collaborative; GlobalSurg Collaborative. Timing of surgery following SARS-CoV-2 infection: an international prospective cohort study. Anaesthesia. 2021 Mar 9. doi: 10.1111/anae.15458. Epub ahead of print. PMID: 33690889. https://pubmed.ncbi.nlm.nih.gov/33690889/ 

Question: What is the optimal timing of surgery after SARSCoV2 infection to reduce 30-day post-op mortality (primary outcome) and pulmonary complications (secondary outcome)? This study was funded by the NIHR, Global Research Group. 

Comparison: This was an observational, international, multicenter prospective cohort study with 140,231 patients of all ages undergoing surgery of which 3,127 (2.2%) patients had SARSCoV2 as confirmed by labs, imaging, or clinical diagnosis. Outcomes were assessed based on timing from diagnosis of SARSCoV2 infection to date of surgery (0-2 weeks, 3-4 weeks, 5-6 weeks, or ≥7 weeks). 

Results: Compared with patients who did not have a pre-operative diagnosis of COVID19, thirty-day post-op mortality was significantly elevated from zero through six weeks (OR ranging 3.6-4.1) among patients with a history of SARSCoV2 infection, but not for those more than 7 weeks since diagnosis. Adjusted 30-day mortality in patients without SARSCoV2 was 1.5% (95%CI 1.4-1.5) and was similar in patients with SARSCoV2 beyond 7 weeks after diagnosis. Patients with ongoing SARSCoV2 symptoms beyond 7 weeks also had increased 30-day post-op mortality. Post-op pulmonary complications were increased in all SARSCoV2 patients especially in weeks zero through six. Older sicker patients had higher mortality.

Bottom Line: This study suggests that patients should wait at least 7 weeks after confirmed SARSCoV2 infection before undergoing elective surgery to mitigate post-op mortality and pulmonary complications. Those who still have symptoms beyond 7 weeks should wait until symptoms resolve. 

Hotcakes rating: B – Half Stack

Links

DARK tv series (Netflix) -Adnan’s pick

Goals

Listeners will review recent practice-changing articles on GLP1 agonists for weight loss, amoxicillin-clavulanate for diverticulitis, and perioperative risk after COVID19 infection

Learning objectives

After listening to this episode listeners will…

1. Discuss the efficacy of semaglutide for weight loss 
2. Compare the efficacy of amoxicillin-clavulanate vs fluoroquinolone based therapy for diverticulitis
3. Recognize the perioperative risk and counsel patients undergoing surgery after COVID19 infection

Disclosures

Drs. Khan, Watto, Williams, and Ganatra report no relevant financial disclosures. 

Citation

Watto MF, Ganatra RB, Khan A, Williams PN. “#264 Hotcakes: Semaglutide for weight loss, Abx for Diverticulitis, Periop COVID19”. The Curbsiders Internal Medicine Podcast. http://thecurbsiders.com/episode-list Final publishing date March 29, 2021.