The tesamorelin cognitive study known as SMART found a modest advantage on tests of attention, task switching and working memory in older adults. It did not establish dementia prevention or better everyday memory.
The question behind SMART
SMART stands for Somatotrophics, Memory, and Aging Research Trial. Could stimulating the body's own growth hormone improve thinking skills as people age?
The paper's title says GHRH, short for growth hormone–releasing hormone, the signal that prompts growth hormone release. The pituitary, a small hormone gland beneath the brain, responds to that signal. The methods identify the drug as tesamorelin. Baker and colleagues published the trial in Archives of Neurology in 2012. The broader guide to what tesamorelin does explains that hormone pathway.
Who took part, and for how long?
The published study assigned 152 adults aged 55–87 to treatment by chance: 86 with normal thinking skills and 66 with mild cognitive impairment. That means memory problems beyond what's usual for someone's age, as NIA's guidance on MedlinePlus explains.
The SMART registry, NCT00257712, records 151 participants; the paper counts 152 randomized and 137 who finished treatment. The counts differ by one.
At the University of Washington in Seattle, 78 participants received tesamorelin and 74 received placebo, an inactive comparison treatment. Participants and staff doing the thinking tests were blinded, meaning they did not know the assigned treatment.
The trial protocol used 1 mg injected under the skin daily, 30 minutes before bedtime, for 20 weeks. Study physicians adjusted treatment when needed. This was a monitored study protocol; a person's prescription dose belongs with their provider.
Diabetes, other neurological illness and already high IGF-1 levels were among the exclusions. IGF-1 is a growth signal made largely by the liver.
What the tesamorelin cognitive study measured
The primary outcome was change in three composite scores, each combining several thinking tests.
Executive function means skills for planning, staying on task and switching between activities, as NIA describes. Tests covered attention, task switching, holding information in mind and producing words.
Verbal memory involved recalling stories and word lists. Visual memory involved remembering designs and their locations. Testing happened before treatment, at weeks 10 and 20, and again 10 weeks after treatment stopped.
Results: executive function had the clearer signal
The combined executive-function score favored tesamorelin over placebo (P=.005). A P value describes statistical evidence for a difference; it does not describe how useful the change felt.
Verbal memory showed a trend (P=.08), which did not meet the usual statistical threshold. Visual memory showed no reliable benefit (P>.15). Calling all three areas improved would overstate the findings.
The overall cognitive comparison favored treatment at week 20 (P=.03) in the analysis based on participants' original treatment assignments. The paper's results describe similar treatment effects in the healthy and impaired groups, without proving separate benefits for every subgroup.
What happened to hormones, body fat and blood sugar?
In SMART, IGF-1 rose 117%, staying within the monitored physiological range, meaning the range normally seen in the body. The paper reports that percent body fat fell by 7.4%.
Insulin, the hormone that helps move blood sugar into cells, rose 35% in fasting samples, collected after not eating. That increase occurred only in participants with impairment. Insulin sensitivity means how readily the body responds to that hormone. Blood sugar and responses to a sugar-drink test did not reliably change. These results do not establish improved insulin sensitivity.
Side effects were more common on tesamorelin
About two in three tesamorelin participants reported side effects, called adverse events in the paper, compared with about one in three on placebo.
| SMART safety finding | Tesamorelin | Placebo |
|---|---|---|
| Participants reporting adverse events, described as mild | 68% | 36% |
| Dose changed because of adverse events | 13 of 78 (17%) | 2 of 74 (3%) |
The paper's safety section lists local redness, itching or stinging and joint aches as the main problems. Less common complaints included stomach upset, hand tingling, weight gain and fluid retention, meaning swelling from extra fluid.
Questions the results left open
The authors described improvements on individual tests as small. They did not collect everyday-function data, so the study cannot show whether people managed appointments, work or household tasks more easily. Most participants were white and had substantial education, limiting how broadly the results apply.
A 2013 commentary by Benedict and colleagues in JAMA Neurology raised another possibility: changes in deep sleep might help explain the scores. SMART used sleep questionnaires rather than laboratory sleep recordings, leaving that explanation unsettled.
What later studies added
The broader tesamorelin trial guide covers the other study settings.
Friedman and colleagues, JAMA Neurology, 2013, studied brain chemistry in 30 SMART participants. Treatment increased GABA, a chemical messenger that helps quiet nerve activity, in the three brain regions examined. Those changes did not significantly track cognitive changes. These were SMART participants; the work did not test the finding in a new trial.
Ellis and colleagues, Journal of Infectious Diseases, 2025, assigned 73 adults by chance to treatment groups. They had HIV—the virus that attacks immune cells—as well as excess belly fat and thinking difficulties. The six-month trial, NCT02572323, compared tesamorelin with usual care; participants knew their treatment and did not receive placebo. The main results reported no significant cognitive-score difference (P=.573), despite a greater waist reduction.
As of October 1, 2026, the day this article was written, a pilot by Stewart and colleagues in eNeurologicalSci had reported no significant overall cognitive improvement. Published June 17, 2026, it analyzed 22 adults after 10 weeks of tesamorelin or placebo. Computer models flagged possible brain-scan differences, which need confirmation. The paper identifies NCT02553603.
How the study gets stretched online
SMART sometimes becomes a claim that tesamorelin is an established thinking enhancer or prevents dementia. A short trial of test performance does not establish either claim.
As of October 1, 2026, the day this article was written, an FDA warning letter dated August 24, 2026 cited online tesamorelin claims about executive function and verbal memory. The agency treated the seller's products as unapproved new drugs, meaning they lacked the required marketing approval. That was an action about those products and their marketing, not a retraction of SMART.
A prescribed route identifies the provider responsible for the decision and the licensed U.S. pharmacy filling it. It also gives the person a pharmacy label and a route to report side effects. Those are concrete details a gray-market listing cannot establish merely by citing a study.
Does adding ipamorelin change the cognitive evidence?
Both compounds aim to prompt the body's own growth hormone release, which explains interest in pairing them. But SMART studied tesamorelin alone. Its results cannot establish what adding ipamorelin does for thinking skills or side effects. The tesamorelin and ipamorelin guide explains the pairing and its evidence gap.
What this means for a person considering treatment
Egrifta WR's prescribing information, marked “Revised: 3/2025,” covers reducing excess abdominal fat in adults with HIV and lipodystrophy, an abnormal pattern of fat distribution. It does not list memory improvement or dementia prevention. The Egrifta label guide walks through its warnings.
Tesamorelin prescribed through Promise is dispensed by a licensed U.S. compounding pharmacy as a compounded medication, which is different from an FDA-approved product: the formulation offered here is not FDA-approved. Compounding means a pharmacy prepares medication for an individual prescription. SMART did not test Promise's compounded preparation.
A licensed provider may still prescribe — that decision is between you and your doctor. A review considers the person's goals, cancer and pituitary history, blood sugar and IGF-1, alongside the limits of the cognitive evidence. At Promise, a licensed provider reviews every request, and not everyone qualifies.
