Common types of SGLT inhibitors 

Empagliflozin – Jardiance  

Dapagliflozin – Farxiga  

Canagliflozin – Invokana  

Sotagliflozin – Inpefa 

What are they and how do they work? 

Sodium-Glucose Linked Transporters (SGLT) are a family of glucose transporters that move glucose across cell membranes. They are located in the small intestine and the kidneys where they retain (or reabsorb) glucose.  Therefore, SGLT inhibitors prevent the kidneys from absorbing as much glucose, which means more glucose is removed through in the urine and overall blood glucose levels are lowered.   

In addition to improving blood glucose, these drugs also provide benefits such as weight loss, blood pressure reduction, and benefits to the heart and kidneys.  

These medications are typically once-daily oral medications. The benefits of the medication are only present while taking them continuously and therefore they are intended for long-term management. The side effects of these medications are mild, so discontinuation rates are relatively low.  

Who can take these medications? 

Despite demonstrating improved glucose control for people with T1D, SGLT inhibitors have not been approved for people with T1D due to the increased risk of diabetic ketoacidosis (DKA). Breakthrough T1D’s priority is to find ways to mitigate this risk so people with T1D can also take advantage of the heart and kidney benefits of SGLT inhibitors.  

Research  

Ongoing research is investigating the benefits of these medications in people with T1D, as well as risk mitigation such as the use of ketone monitoring. The introduction of continuous ketone monitors may provide effective risk mitigation to support regulatory approval for people with T1D to use SGLT inhibitors. There has been little to no research investigating the cardiovascular benefits of SGLT inhibitors in people with T1D, which is an area of research that warrants more investigation. 

Breakthrough T1D is currently funding the SUGARNSALT trial to assess the benefits of sotagliflozin on kidney function and the safety profile of a DKA prevention program. This trial is recruiting internationally, including in Canada. For an up-to-date listing of Canadian clinical trials for SGLT inhibitors, visit our T1D Clinical Trial Finder. 

Canadian spotlight: ATTEMPT Study  

A Breakthrough T1D-funded study known as ATTEMPT (The Adolescent Type 1 Diabetes Treatment with SGLT2i for hyperglycEMia & hyperfiltration Trial) aimed to determine the safety and efficacy of the SGLT inhibitor dapagliflozin on the management of blood glucose and kidney function in adolescents with T1D. Led by Dr. Farid Mahmud, pediatric endocrinologist at SickKids hospital in Toronto, Canada, the 16-week study involved 98 participants aged 12-18. The study included a rigorous monitoring protocol to ensure the safety of participants, including regular ketone checks and assessments to manage dehydration risks.  

RESULTS: A low dose of dapagliflozin safely improved glycemic management (HbA1c) and kidney function (glomerular filtration rate) without additional adverse risks when used with monitoring protocols. 

Metformin 

• How the drug works: Metformin is an antihyperglycemic agent that decreases glucose production in the liver, increases the sensitivity of body tissues to insulin thereby promoting the use of glucose by cells, reducing appetite. 

• Example: Metformin is available as a generic medication (i.e., its not under patent) but is still sometimes sold under brand names such as Glucophage and Glumetza in Canada. It is on the World Health Organization’s List of Essential Medicines.  

• What’s known so far: Metformin has been approved for T2D since the 1990s and is used commonly off-label (i.e., in a non-approved population at physician discretion) for people with T1D, particularly where weight is also a concern. Metformin is one of the most commonly prescribed medications globally. Many large studies have found that metformin can reduce HbA1c, weight, and insulin doses in people with T1D, without an increased risk of hyperglycemia or DKA. However, it can be accompanied by gastrointestinal side effects. It has also been studied widely in adolescents and Diabetes Canada’s Clinical Practice Guidelines recommend that it can be considered for adolescents with T1D. 

• Future: Although metformin’s impact on HbA1c has been considered too small to warrant approval for individuals with T1D, it is widely prescribed at a physician’s discretion. It can support weight management alongside T1D but does not significantly improve blood glucose control. There has been some ongoing research into the cardiovascular benefit for people with T1D, but to date, no compelling evidence that it is effective at reducing cardiovascular complications.  

Glucokinase activators 

• How the drug works: Glucokinase is an enzyme in the liver and pancreas that acts as a ‘glucose sensor’. It triggers beta cells to release insulin and it converts glucose to a more usable form – getting it ready to be stored in the liver or used by cells.  Glucokinase activators “turn on” glucokinase to help lower blood glucose levels. 

• Example: Cadisegliatin (TTP399), developed by vTv Therapeutics with funding from Breakthrough T1D. 

• What’s known so far: In the phase II Simplici-T1 trial (2017), cadisegliatin improved HbA1c, reduced insulin dose, lowered hypoglycemia, and did not increase DKA.  

• Future: A phase III trial is now underway in the US 

Glucagon receptor antagonists 

• How the drug works: Glucagon is a hormone made by alpha cells in the pancreas that tells the liver to release stored glucose into the blood, thereby raising blood glucose. In T1D, alpha cells are also impaired and do not release glucagon in response to low blood glucose. Glucagon receptor antagonists block this signal, preventing the liver from releasing excess glucose.  

• Example: Volagidemab, an antibody that binds the glucagon receptor and blocks the signal. 

• What’s known so far: A phase II clinical trial in people with T1D showed volagidemab lowered HbA1c and reduced insulin use by 15%. 

• Future: A phase III trial is now underway in the US. 

Somatostatin inhibitor 

• How the drug works: Somatostatin type 2 (SSTR2) receptors are located on alpha cells in pancreatic islets. In people with T1D, too much somatostatin is released during hypoglycemic episodes, which blocks the production of glucagon to raise blood glucose levels and avoid or recover from a hypoglycemic episode. ZT-01 blocks the SSTR2 receptors on the alpha cells so that glucagon can be released when blood glucose levels drop. 

• Example: Zucara Therapeutics is developing ZT-01, a first-in-class, once-daily therapeutic to prevent insulin-induced hypoglycemia in patients using insulin therapy. This company is funded by the T1D Fund: a Breakthrough T1D Venture. 

• What’s known so far: A phase I study determined the safety of this drug in healthy volunteers and people with T1D, as well as the efficacy to improve glucagon release. 

• Future: A phase II study is ongoing to determine the efficacy of ZT-01 on nighttime hypoglycemic episodes in adults with T1D. 

Amylin replacement 

• How the drug works: Amylin is a hormone produced by pancreatic beta cells alongside insulin. In people with T1D, the production of amylin is also impacted by the autoimmune attack. Amylin responds to nutrient stimuli to help regulate glucose levels after eating, slowing gastric emptying and supressing glucagon to avoid further increasing blood glucose levels. 

• Example: Pramlintide is an engineered form of amylin. It is approved in the US for people with T1D but not in most other countries, including Canada, due to an increased risk of hypoglycemia. 

• What’s known so far: Studies have shown that the addition of pramlintide post-meal can reduce HbA1c, weight, total insulin dose, and post-meal glucose levels; however, adverse effects include nausea, vomiting, anorexia, and hypoglycemic episodes. 

• Future: Research is ongoing to investigate varying levels of pramlintide given in conjunction with automated insulin delivery (AID) to reduce the need for carb counting while improving glucose management. 

For an up-to-date listing of Canadian clinical trials for adjunct therapies, visit our T1D Clinical Trial Finder. 

There are currently more than 40 clinical trials in GLP-1RA and SGLT inhibitor therapies underway. Below are a few examples of Breakthrough T1D-funded clinical trials and/or trials ongoing in Canada for adults with T1D: 

*Updated November 2025 

For an up-to-date listing of Canadian clinical trials for adjunct therapies, visit our T1D Clinical Trial Finder.