Background and Aims / Part 1

Patients with type 1 diabetes are facing the sobering outlook that today despite improvements in insulin therapy they are prone to increased cardiovascular mortality. The onset of type 1 diabetes before age 10 has been associated with 17 years loss of life in girls and 14 years in boys. In addition, increasing incidence of overweight, hypertension and negative psychosocial consequences due to unpredictable glucose swings are other unmet needs that potentially can be addressed by adjunct therapy with SGLT inhibitors.

Methods / Part 2

Dapagliflozin and sotagliflozin have been approved for adjunct therapy in certain patients with type 1 diabetes in Europe. In Germany, the Federal Joint Committee (G-BA), the highest decision-making body of the joint self-government of physicians, hospitals and health insurance funds, has recently issued a positive benefit assessment for dapagliflozin. Also, in the UK, the cost-effectiveness estimate for dapagliflozin plus insulin compared with insulin alone was judged to be within the range that NICE normally considers an acceptable use of NHS resources. Certainly this therapy is not suited for every patient with type 1 diabetes.

Results / Part 3

Current prerequisites for adjunct therapy with SLT inhibitors include a body mass index (BMI) of at least 27 kg/m², when insulin alone does not provide adequate glycemic control despite optimal insulin therapy, and if patients have completed a structured education program about diabetic ketoacidosis. Treatment should be started and supervised by a consultant physician specializing in diabetes. Evidence from the clinical trials show small improvements in HbA1c levels and increases of up to 3 hours time in range by CGM as well as an average weight loss of 3kg in overweight individuals, and improvements in quality of life, when SGLT inhibitors plus insulin are compared with placebo plus insulin in adults with type 1 diabetes.

Conclusions / Part 4

Thus, adjunct therapy should be initiated in adults with type 1 diabetes if an individual risk / benefit assessment as outlined above indicates the likelihood of positive outcomes.

Background and Aims

Insulin treatment of persons with type 1 diabetes has shortcomings and many patients do not achieve glycaemic and metabolic targets. Consequently, the focus is on novel non-insulin therapeutic approaches that reduce hyperglycaemia and improve metabolic variables without increasing the risk of hypoglycaemia, weight gain or other adverse events. Several therapies given in conjunction with insulin have been investigated in clinical trials, including dipeptidyl peptidase-IV (DPP-IV) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists. These drugs have pleiotropic effects on glucose metabolism and different actions complementary to those of insulin.

Overall, DPP-IV inhibitors added to insulin treatment in persons with type 1 diabetes have shown a modest, but non-clinically relevant reduction in HbA1c with no raised risk of hypoglycaemia and no effect on body weight have been reported. More promising, a significant reduction in body weight and daily insulin dose combined with reductions in HbA1c have been reported with the use of GLP-1 receptor agonists in type 1 diabetes.

Both DPP-IV inhibitors and GLP-1 receptor agonists seem to be well tolerated, however symptomatic hypoglycaemia and hyperglycaemia with ketosis when adding a GLP-1 receptor agonist to insulin in type 1 diabetes have been reported.

Currently, there are no DPP-IV inhibitors, nor GLP-1 receptor agonists approved for the treatment of type 1 diabetes – should there be?

Background and Aims / Part 1

Application of adjunctive therapies for treatment of type 1 diabetes (T1D) has been an area of intense exploration. However, prior to the recent approval of the dual SGLT1/2 inhibitor in Europe, the sole therapy approved for those with T1D had been pramlintide. Garnering approval from the FDA in 2005, pramlintide has had limited penetrance into clinical practice, potentially due to the need for multiple daily subcutaneous injections to administer it. To overcome this issue, some have explored co-formulation of pramlintide with insulin analogues. This presentation will review the mechanism of action of pramlintide, studies describing its use in those with T1D, and examine how co-formulation has altered the potential to integrate this therapy, even in automated insulin delivery systems.

Methods / Part 2

Additionally, the role of metformin in treatment of T1D will also be reviewed focusing on the mechanism of action, studies of the agent in those with T1D, with particular focus on its effects on long-term risk of cardiovascular disease.