ACHIEVE-2 and ACHIEVE-5 succeed

Eli Lilly reported that orforglipron, an experimental once-daily oral GLP-1 receptor agonist, met the main goal in two more Phase 3 type 2 diabetes trials. In ACHIEVE-2, the pill lowered A1C by up to 1.7% compared with 0.8% for dapagliflozin. In ACHIEVE-5, it lowered A1C by an additional 2.1% when taken alongside insulin glargine ^[1].

Both results are primary endpoint wins, meaning the trials hit the specific statistical target they were designed to test ^[1]. Together they extend a run of positive results for the drug across different stages of type 2 diabetes treatment.

What the trials showed

ACHIEVE-2 pitted orforglipron against dapagliflozin, an oral diabetes medicine, rather than against a sugar pill. That head-to-head design matters because it compares the new drug with something patients actually take. The reported A1C drop was up to 1.7% for orforglipron versus 0.8% for dapagliflozin ^[1].

ACHIEVE-5 tested the pill in people already using basal insulin. Adding orforglipron to insulin glargine produced an extra 2.1% A1C reduction ^[1]. People who need insulin often have longer-standing diabetes and higher blood sugar, so an added-on oral option is a different question from first-line treatment.

The announcement did not include, in the material available here, trial sizes, treatment length, dose-by-dose breakdowns, weight change or detailed side effect rates for these two studies. Those figures are not yet known from this source ^[1].

For context, earlier Phase 3 work gave more detail. In ACHIEVE-1, orforglipron at 3 mg, 12 mg and 36 mg as a standalone treatment lowered A1C by an average of 1.3% to 1.6% from a baseline of 8.0% at 40 weeks versus placebo, more than 65% of people on the highest dose reached an A1C of 6.5% or lower, and average weight loss at the highest dose was 16.0 pounds, or 7.9% ^[1]. Lilly said the safety and tolerability profile in that trial was consistent with injectable GLP-1 medicines ^[1].

In a Phase 2 diabetes study, orforglipron cut A1C by up to 2.1% versus 0.4% with placebo and 1.1% with dulaglutide at 26 weeks ^[1].

Why it matters for patients

Most GLP-1 drugs used for type 2 diabetes today are injections. Orforglipron is a small-molecule, non-peptide GLP-1 receptor agonist taken as a tablet ^[1]. If a pill can deliver A1C reductions in the same range as injectables, it changes the menu of options for people who dislike needles or who struggle with the cold-chain and pharmacy logistics of injectable pens.

The ACHIEVE-2 and ACHIEVE-5 designs speak to two common real-world situations: someone choosing between oral diabetes drugs, and someone whose insulin alone is not getting their A1C to goal. Beating an active comparator and adding benefit on top of insulin are different kinds of evidence than beating placebo.

Important caveats remain. These are company announcements of topline results, not peer-reviewed publications, and the detailed safety data for these two trials are not in this source ^[1]. GLP-1 drugs in this class carry known risks; orforglipron's later labeling includes a boxed warning for thyroid C-cell tumors and warnings covering pancreatitis, severe gastrointestinal reactions, kidney injury from fluid loss, low blood sugar, gallbladder disease and diabetic retinopathy complications, with nausea, constipation, diarrhea and vomiting among the most common side effects ^[1].

What happens next

Lilly's oral GLP-1 went on to post more Phase 3 results. In ACHIEVE-3, orforglipron 36 mg lowered A1C by 2.2% versus 1.4% with oral semaglutide 14 mg, and produced 19.7 pounds (9.2%) of weight loss versus 11.0 pounds (5.3%) ^[1]. In ACHIEVE-4, it met non-inferiority against insulin glargine on cardiovascular outcomes ^[1].

The FDA approved the drug as Foundayo on April 1, 2026 — but for weight management in adults with obesity or overweight with a weight-related condition, based on the ATTAIN program, not for type 2 diabetes ^[1]. Orforglipron is described as still being studied as a potential diabetes treatment ^[1].