A Phase 3 trial design for combining semaglutide, an SGLT2 inhibitor, and insulin in type 1 diabetes

This paper describes the plan for a clinical trial, not its findings. Published in Diabetes, Obesity & Metabolism, it lays out the design and methods of TTT1, described as the first Phase 3 trial to test adding two newer diabetes medicines to insulin in adults with type 1 diabetes. It is a study in people, not in animals or cells.

Because it is a design and methods report, there are no efficacy or safety outcomes to summarize here. The authors explain who they are recruiting, how participants are grouped, and what they intend to measure. What the treatments actually did will come in later publications, not this one.

The problem the trial is trying to address

In type 1 diabetes, hitting target blood sugar is hard, partly because insulin can drive weight gain. The authors note that medicines developed for type 2 diabetes have potential as add-on therapy but may not be strong enough on their own and carry risks such as low blood sugar and ketosis. TTT1 was designed to study that trade-off directly.

Who is being studied and how

The trial enrolls overweight and obese adults with type 1 diabetes whose glucose is above target, defined by an HbA1c between 7.5% and 11.0%. HbA1c is a blood marker that reflects average glucose over roughly three months.

The design runs in two periods. In the first 26 weeks, participants are randomized 2 to 1, in open-label fashion, to either semaglutide plus insulin or standard insulin therapy. In the second 26 weeks, those who were on semaglutide plus insulin are randomized again, this time double-blind, to add either an SGLT2 inhibitor called dapagliflozin or a placebo.

What the researchers plan to measure

The main comparison is the change in HbA1c on triple therapy, meaning dapagliflozin plus semaglutide plus insulin, versus dual therapy, meaning placebo plus semaglutide plus insulin. Secondary comparisons include each combination against standard insulin therapy alone. Safety tracking focuses on hypoglycaemia and ketosis, the two risks the authors flag up front.

The registered trial identifier is NCT03899402. During the study, a sample size recalculation using masked data lowered the recruitment target from 114 to 82 participants.

What this does and does not establish

This publication establishes a plan and a rationale. It does not establish that any of these combinations lowers HbA1c, reduces weight, or is safe in type 1 diabetes, because results are not part of a design paper. It also does not speak to type 2 diabetes or to weight management on their own. Nothing here should be read as evidence that a specific combination will work for any individual, and outcomes in any trial vary from person to person.

One honest limitation

Beyond the fact that no results are reported, the change from 114 to 82 planned participants is worth noting. A smaller sample can still answer a well-defined question, but it narrows the statistical power to detect smaller effects and to characterize less common safety events. How that plays out will only be clear when the completed trial is published.

Why this matters for someone considering care

Semaglutide is a GLP-1 medication that Live Vital offers, but the population and setting in this trial are specific: adults living with type 1 diabetes, studied under a controlled research protocol with insulin. That is a different context from off-label use in other situations, and it is not a template for self-directed treatment.

If you want a physician to weigh in on your situation, semaglutide through Live Vital is physician-prescribed and requires a medical intake and physician approval, which you can begin at /get-started. A prescription is never guaranteed. Live Vital does not accept insurance, though HSA and FSA funds may be used.