Research library

A

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In obese adults, orforglipron 36 mg shows statistically significant improvements in weight and metabolic outcomes compared to 12 mg, but the clinical significance of these findings requires further investigation.

Percentage body weight change p < 0.00001.

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A

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Orforglipron was associated with significant reductions in predicted 10-year risks for Type 2 diabetes and cardiovascular disease compared to placebo over 72 weeks, but the clinical relevance of these findings needs further evaluation.

-48.6% to -59.4% relative reduction in T2D risk score vs placebo (-10.5%; p<0.0001; HR-range 0.43-0.55)

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D

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Orforglipron shows promise in reducing certain metabolic parameters, but its effects on kidney health remain uncertain until further trials specifically address renal outcomes.

Not reported in abstract.

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B

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The AHA PREVENT equations may offer a more comprehensive assessment of cardiovascular risk reduction from orforglipron compared to the older PCE. These projections should be validated with future cardiovascular outcomes trials.

For a representative 50-year-old man with T2D, the PCE estimated a 10-year RRR of 16.8% at the 36 mg dose, while PREVENT projected an RRR of 31.4% at the same dose.

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C

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The study reveals that GLP-1R variants can enhance orforglipron binding, but this does not guarantee effective pharmacological action, highlighting the need for further validation.

G168S exhibited the strongest binding (-117.18 kcal/mol)

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B

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Orforglipron resulted in a placebo-subtracted weight loss of -12.4% in adults without diabetes, but gastrointestinal side effects were common.

-12.4% placebo-subtracted weight loss for orforglipron (95% CI, -15.1% to -9.7%)

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A

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Orforglipron showed a high rate of treatment-emergent adverse events in Japanese adults with type 2 diabetes, particularly at higher doses, indicating caution in its use.

339 participants (85%, 95% CI 80·7-87·8) had at least one treatment-emergent adverse event (TEAE).

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D

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Not reported in abstract.

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A

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Not reported in abstract.

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D

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Not reported in abstract.

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A

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Orforglipron was associated with significant weight loss in older adults with obesity compared to placebo at Week 72, but the clinical relevance of the findings should be carefully considered.

-7.9% weight change with orforglipron 5.5 mg vs placebo at Week 72, n=118, p<0.001.

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A

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Orforglipron does not appear to increase the risk of drug-induced liver injury compared to other treatments in adults with obesity or type 2 diabetes.

Six (0.1%) orforglipron-treated participants had ALT or AST ≥ 3 × ULN and TBIL ≥ 2 × ULN.

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A

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Orforglipron showed a mean weight reduction of -11.8% compared to placebo, but evidence certainty was low to moderate.

-11.8% percent body weight reduction for orforglipron compared to placebo.

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D

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Not reported in abstract.

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D

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Not reported in abstract.

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A

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Orforglipron significantly improved HbA1c levels and body weight in adults with type 2 diabetes inadequately controlled by insulin glargine, without increasing hypoglycemia risk.

-1.58%, -1.88%, and -1.82% HbA1c change with orforglipron 3 mg, 12 mg, and 36 mg respectively at week 40, n=546.

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D

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Not reported in abstract.

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A

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Orforglipron (OFG) demonstrated significant reductions in body weight and improvements in glycemic outcomes, particularly at the 45 mg dose, but further long-term studies are needed to confirm these findings.

MD: -12.13 kg at 36 weeks, n=4878, p<0.001 for 45 mg vs placebo.

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B

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Orforglipron shows potential neuroprotective and anti-inflammatory effects in vitro, but its low brain uptake in rats raises questions about its clinical relevance for neurological conditions.

Brain/plasma and CSF/plasma ratios: 0.0078.

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A

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Orforglipron may lead to significant weight loss and improvements in glycemic control, but gastrointestinal side effects may increase with higher doses.

-1.29% HbA1c, n=6140.

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B

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Oral semaglutide 25 mg was associated with greater body weight loss and fewer discontinuations due to adverse events compared to orforglipron 36 mg, but these findings are based on indirect comparisons.

-3.2%-points (95% CI: -5.9, -0.4; treatment-regimen estimand)

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A

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ATTAIN-OSA is investigating whether oral orforglipron can serve as a more accessible treatment for moderate-to-severe obstructive sleep apnea in adults with obesity or overweight.

Not reported in abstract.

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B

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About 25% of participants were unwilling to take a weekly injectable obesity medication and significantly preferred a daily oral option over a weekly injection.

RAI: 62.7% for mode/frequency of administration.

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A

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Orforglipron showed a statistically significant reduction in body weight in adults with type 2 diabetes compared to placebo, but the clinical relevance of this weight loss is uncertain.

-9.6% bodyweight change with 36 mg orforglipron at week 72, p<0.0001.

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D

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Not reported in abstract.

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