HOMA-IR Explained: What Your Score Means

HOMA-IR explained in everyday terms: it estimates how much insulin your body needs to keep blood sugar steady while fasting. Insulin is the hormone that helps cells use blood sugar. Fasting means a period without food.

A higher score usually suggests greater resistance to insulin's signal. There is no universal normal range, and the score doesn't diagnose diabetes by itself.

HOMA-IR explained: the formula and units

HOMA stands for homeostasis model assessment. Matthews and colleagues introduced the model in Diabetologia in 1985. Its resistance estimate uses fasting glucose, meaning blood sugar, and fasting insulin from blood samples.

The simple equation's divisor depends on the glucose units. Published study methods reproduce both versions:

Insulin's mU/L means milliunits per liter; it has the same numerical value as μIU/mL, another common lab unit. HOMA-IR itself has no units.

For example, glucose of 5 mmol/L and insulin of 10 mU/L give 50 ÷ 22.5, or about 2.22. That calculation alone doesn't establish a diagnosis.

What tirzepatide changed in SURMOUNT-1

HOMA2-IR uses an updated computer model rather than the simple equation above. The Matsuda index estimates insulin sensitivity using blood tests before and after a glucose drink. Higher Matsuda values mean greater sensitivity; lower HOMA resistance values generally mean less resistance.

A clamp is a more involved test that infuses insulin and glucose to measure the body's response. These methods examine related questions, but their scores aren't interchangeable.

Mari and colleagues' 2025 Diabetes Care analysis of SURMOUNT-1 studied adults with excess weight without diabetes over 72 weeks. The trial randomized 2,539 people. In that trial, Figure 3 printed these rounded average changes, adjusted for starting measurements and other factors:

These are changes in a sensitivity score, not percentages or HOMA-IR point drops. The paper also reported falling HOMA2-IR across tirzepatide doses. Much of the sensitivity improvement was associated with weight loss.

These doses were study assignments; a prescriber sets an individual's dose. The tirzepatide diabetes guide covers its separate blood-sugar trials.

HOMA-IR normal range: why cutoffs disagree

A laboratory's insulin assay, the test it uses to measure insulin, affects the result. So do the population studied and the question being asked. Wallace's 2004 Diabetes Care review explains why HOMA needs reliable measurements and careful interpretation.

The EPIRCE study, published in BMC Endocrine Disorders in 2013, examined 2,459 Spanish adults. Its figures illustrate the problem:

Those are population-specific research thresholds. Age changed the test's performance in women without diabetes; results differed by sex too. Neither number is a universal treatment target.

As of October 29, 2026, the day this article was written, a September 28 expert report in Diabetologia reinforces this caution. It describes insulin resistance as varying across organs and circumstances. HOMA remains an indirect estimate that belongs beside the rest of the clinical picture.

MOTS-c: mouse findings and an unanswered human question

MOTS-c is a peptide, a short chain of protein building blocks, linked to mitochondria, the structures that help cells produce energy. Lee's 2015 Cell Metabolism study reported insulin-sensitivity findings in mice. Those experiments don't supply a human HOMA-IR improvement figure.

As of October 29, 2026, the day this article was written, NCT07505745 is listed as recruiting, with no posted results. This sponsor-submitted trial record names change in the Matsuda index among its main outcomes. A registration describes a plan, not evidence that treatment worked.

As of October 29, 2026, the day this article was written, HHS's notice filed October 28 announces a draft compounding policy covering six peptides, including MOTS-c. It is a draft, non-binding enforcement policy, not an approval: HHS says it “does not intend to take enforcement action” on this compounding “when all of the following circumstances are present” — ten conditions in all. The HHS policy explainer covers the details.

MOTS-c is not FDA-approved. That status and the policy do not establish an insulin-resistance benefit in people.

Semaglutide: what a 28% difference means

STEP 1 included participants with prediabetes, blood sugar above normal but below diabetes levels. In that group, semaglutide 2.4 mg had an estimated relative HOMA-IR difference versus placebo of −28% at 68 weeks. That comes from Perreault and colleagues' 2022 Diabetes Care analysis.

It doesn't mean HOMA-IR fell 28 points. It also doesn't rank semaglutide against the Matsuda results above: the studies used different measurements and analyses. The broader peptides for insulin resistance guide compares the evidence behind the medicines.

Tesamorelin: why blood sugar needs its own attention

Tesamorelin stimulates release of growth hormone, which affects growth and how the body uses fuel. Its branded Egrifta WR label concerns excess abdominal fat in adults with HIV-associated lipodystrophy, meaning altered fat distribution. HIV is a virus that weakens immune defenses.

The FDA label, marked “Revised: 3/2025,” warns that treatment can impair glucose handling; the Egrifta prescribing-information guide walks through the rest of the label. Section 5.4 reports these figures from the clinical trials through week 26:

That's about 5 in 100 versus 1 in 100. A1C, also called HbA1c, reflects average blood sugar over roughly three months. It measures something different from fasting insulin or HOMA-IR.

Falutz's 2007 NEJM trial reported no significant between-group difference in glucose and insulin measures. An average result doesn't exclude a blood-sugar problem in some participants. The label calls for glucose assessment before and during treatment.

How the numbers fit the prescribing conversation

A clinician reads HOMA-IR alongside fasting glucose, A1C and history. The A1C explainer covers what changes in that separate measurement mean. One lower score doesn't answer every treatment question.

Tirzepatide, semaglutide and tesamorelin prescribed through Promise are dispensed by a licensed U.S. compounding pharmacy as compounded medications. This is different from an FDA-approved product: the formulations offered here are not FDA-approved. FDA explains that compounded drugs aren't reviewed for safety, effectiveness or quality before marketing. Brand trial results don't establish identical outcomes for compounded preparations.

A licensed provider may still prescribe — that decision is between you and your doctor. At Promise, a licensed provider reviews every request, and not everyone qualifies.