📘 TLDR Primary Care - Journal Club (#044)

In This Issue:

💊 Our PC study of the month: Oral GLP-1s for glycemic control in type 2 diabetes

❄️ Roflumilast in patients with Seborrheic Dermatitis

🦠 Spironolactone in women with Acne Vulgaris

🫘 Can dapagliflozin be useful for anemia in patients with CKD?

🫁 A biologic for patients with COPD and increased eosinophil counts

💤 Could melatonin be helpful in IBS?

📘 Journal Club: Fresh Off the Press

Bringing you the latest practice-changing updates in primary care

✅ Study of the Month: Oral GLP-1 receptor agonists for the treatment of type 2 diabetes

💊 Can GLP-1 receptor agonists be taken orally for glycemic control in type 2 diabetes?

• The Oral GLP-1 trial (May 2023, n=411) compared danuglipron orally at a dose of 2.5, 10, 40, 80, or 120 mg administered twice daily with food for 16 weeks to a matching placebo in adults with T2DM inadequately controlled by diet and exercise, with or without metformin treatment. The key exclusion criteria included T1DM, a recent history of cardiovascular events, gastrointestinal conditions possibly affecting drug absorption, and medullary thyroid carcinoma. We will cover two of the five trial arms below with the 40 mg and 120 mg doses.

• Danuglipron 40 mg twice daily
  • There was a significant decrease in Hemoglobin A1c at week 16 (1.03% vs. 0.02%; MD 1.01, 90% CI 0.73 to 1.3). One of the secondary outcomes included a significant increase in the reduction of fasting plasma glucose at week 16 (30.47 mg/dL vs. -1.31 mg/dL; MD 31.78, 90% CI 20.35 to 43.2)
• Danuglipron 120 mg Twice Daily
  • There was a significant decrease in Hemoglobin A1c at week 16 (1.18% vs. 0.02%; MD 1.16, 90% CI 0.86 to 1.47, NNT= 86). One of the secondary outcomes included a significant increase in reduction of body weight at week 16 (4.6 kg vs. 0.43 kg; MD 4.17, 90% CI 3.18 to 5.15).

Conclusion: In adults with poorly controlled T2DM danuglipron was superior to placebo with respect to reduction in Hemoglobin A1c at week 16. At a dose of 120mg twice daily, danuglipron was also superior to placebo in the reduction of body weight at week 16. 

You’ll find more of the latest studies relevant to primary care below. For a more comprehensive catalog of recent practice-changing trials, head over to Pathway!

❄️ What is the role of roflumilast in patients with seborrheic dermatitis?

• The Roflumilast in SD trial (May 2023, n=226) compared once-daily roflumilast foam at a dose of 0.3% to a matching placebo vehicle foam for 8 weeks in adult patients with a clinical diagnosis of seborrheic dermatitis for ≥ 3 months and Investigator Global Assessment (IGA) score of ≥ 3, affecting ≤ 20% of the body. Patients were required to stop topical antifungals, corticosteroids, and numerous other medications ≥ 2 weeks before randomization to be included in the study. 

• The primary outcome showed a significant increase in patients achieving IGA success compared to baseline at week 8 (73.8% vs. 40.9%; AD 32.8%, 95% CI 18.5 to 45.7, NNT=3). One of the secondary outcomes showed a significant increase in patients achieving erythema success at week 8 (44.7% vs. 21.2%; AD 23.5%, 95% CI 9.6 to 35). There was no significant difference in adverse events.

Conclusion: In adult patients with a clinical diagnosis of seborrheic dermatitis roflumilast foam was superior to vehicle foam with respect to IGA success at week 8.

🦠 What is the role of spironolactone in women with acne vulgaris?

• The SAFA Trial (May 2023, n=342) investigated the effectiveness of oral spironolactone at a dose of 50 mg per day compared to a matching placebo until week six, increasing to 100 mg per day spironolactone or matching placebo until week 24. This was done in adult women with facial acne for at least 6 months and judged to warrant oral antibiotic treatment. The key exclusion criteria included previous use of spironolactone, use of isotretinoin in the past 6 months, or use of oral antibiotics for > 1 week for acne within the previous month.

• The primary outcome was a small but significant increase in the Acne-Specific Quality of Life symptom subscale score at week 12 (19.2 vs. 17.8; AD 1.27, 95% CI 0.07 to 2.46). A secondary outcome showed a significant increase in the Acne-Specific Quality of Life symptom subscale score at week 24 (21.2 vs. 17.4; AD 3.45, 95% CI 2.16 to 4.75). More patients in the spironolactone group had at least one adverse reaction (64% vs. 51%) but there were no serious adverse reactions.

Conclusion: In adult women with facial acne, spironolactone was superior to placebo with respect to improvement in Acne-Specific Quality of Life symptoms subscale score at week 12, with even more improvement seen at week 24.

🫘 What is the role of dapagliflozin in correcting and preventing anemia in patients with CKD?

• The DAPA-CKD post-hoc analysis (May 2023, n=4292) compared dapagliflozin at a dose of 10 mg per day to a matching placebo in adult patients that have CKD with and without anemia. The key exclusion criteria included T1DM, polycystic kidney disease, LN, or ANCA-associated vasculitis. 

• The primary outcome showed a significant increase in hematocrit improvement during follow-up (2% vs. -0.3%; AD 2.3%, 95% CI 2.1 to 2.5). One of the secondary outcomes showed a borderline significant increase in the correction of anemia in patients with anemia (53.3% vs 29.4%; HR 2.29, 95% CI 1.96 to 2.68). Another secondary outcome showed a borderline significant decrease in incident anemia in patients without anemia (10.4% vs. 23.7%; HR 0.39, 95% CI 0.31 to 0.48). There was no significant difference in adverse events. 

Conclusion: In patients with CKD with and without anemia, dapagliflozin was superior to placebo with respect to hematocrit improvement during the 2.4-year median follow-up.

🫁 What is the role of dupilumab in patients with COPD who had type 2 inflammation indicated by eosinophil counts?

• The BOREAS trial (May 2023, n=939) compared dupilumab as a subcutaneous injection of 300 mg every 2 weeks to a matching placebo in adult patients with COPD who had a blood eosinophil count ≥ 300 cells/mL and an elevated exacerbation risk despite the use of standard triple therapy. The key exclusion criteria included a current diagnosis of asthma or a history of asthma. 

• The primary outcome showed a significant decrease in annualized rate of moderate or severe COPD exacerbations (0.78 vs. 1.10; RR 0.70, 95% CI 0.58 to 0.86). One of the secondary outcomes saw a significant increase in improvement of prebronchodilater FEV1 at week 12 (160 mL vs. 77 mL; LSMD 83, 95% CI 42 to 125). There was no significant difference in adverse events.

Conclusion: In patients with COPD who had an elevated eosinophil count and an elevated exacerbation risk despite the use of standard triple therapy, dupilumab was superior to placebo with respect to annualized rates of moderate or severe exacerbations.

💤 What is the effect of melatonin on IBS in patients with or without sleep disorders?

• The Melatonin in IBS trial (Apr 2023, n=136) compared melatonin at a dose of 3 mg BID for 2 months to a matching placebo in adult patients with a diagnosis of IBS based on Rome IV criteria. The groups were split by sleep disorder status, with half of each group receiving the treatment and the other half receiving the placebo. The key exclusion criteria included allergies, side effects, or compromised adherence to the treatment. 

• The primary outcome showed a significant decrease in the number of patients with moderate-to-severe IBS scores in patients with sleep disorders (41.2% vs. 70.6%; RR 0.58, 95% CI 0.08 to 1.08, NNT=3) and without sleep disorders (41.2% vs. 76.5%; RR 0.54, 95% CI 0.07 to 1.01, NNT=3). One of the secondary outcomes saw a significant decrease in quite severe-to-severe abdominal pain in patients with sleep disorders (20.6% vs. 32.3%, RR 0.64, 95% CI 0.05 to 1.23).

Conclusion: In patients with IBS, melatonin was superior to placebo in reducing the number of patients with moderate-to-severe IBS regardless of sleep disorder status.

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