Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2 & 3
Recruiting
Sponsor: State University of New York at Buffalo
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?To assess whether the addition of dapagliflozin to semaglutide and insulin (triple therapy) improves glycemic control in patients with type 1 diabetes compared with semaglutide and insulin (dual therapy) and insulin only (standard) treatment.
What data supports the idea that Triple Therapy for Type 1 Diabetes is an effective treatment?The available research does not provide specific data on the effectiveness of Triple Therapy for Type 1 Diabetes. The studies focus on different treatments and conditions, such as insulin types for Type 1 Diabetes and semaglutide for Type 2 Diabetes. Without direct evidence from these studies, we cannot conclude the effectiveness of Triple Therapy for Type 1 Diabetes.45789
What safety data is available for triple therapy in Type 1 Diabetes?The safety data for components of the triple therapy, such as insulin and dapagliflozin, is available from various studies. Insulin lispro has a safety profile comparable to regular human insulin, with no significant differences in adverse events or progression of diabetes complications. Insulin glargine 300 U/mL has been evaluated for safety in Type 1 Diabetes. However, specific safety data for the combination of dapagliflozin, insulin, and semaglutide in triple therapy for Type 1 Diabetes is not directly addressed in the provided studies.346910
Is the drug Insulin, Semaglutide a promising treatment for Type 1 Diabetes?Yes, Insulin, Semaglutide is promising for Type 1 Diabetes. Studies show it improves blood sugar control after meals and reduces the risk of low blood sugar episodes, especially at night. It also helps patients achieve better overall blood sugar levels, making it a favorable option for managing diabetes.12468
Do I have to stop taking my current medications for this trial?The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have used any diabetes treatment other than insulin in the last 3 months.
Eligibility Criteria
Adults aged 18-70 with Type 1 Diabetes for at least a year, on stable insulin treatment, and regularly monitoring blood sugar can join. They must have a BMI ≥25 kg/m2 and not be on weight loss programs or intensive exercise. Excluded are those with recent severe hypoglycemia, heart issues, kidney failure, liver disease, certain infections or cancers, pregnant women or those not using contraception.Inclusion Criteria
I take at least 0.5 U/kg of insulin for multiple daily injections or 0.4 U/kg for pump therapy.
I have had Type 1 Diabetes for over a year and use an insulin pump or take four or more insulin shots daily.
I check my blood sugar levels at least four times a day.
I am between 18 and 70 years old.
Exclusion Criteria
I have been diagnosed with diabetes or chronic pancreatitis recently or have MODY.
I haven't used diabetes medication other than insulin in the last 3 months.
I have had pancreatitis before.
My diabetes symptoms are not well-managed.
My liver isn't working well, with high AST or ALT levels.
I have a history of delayed stomach emptying.
I've had more than one severe low blood sugar episode needing medical help in the last month.
I am not pregnant, using reliable birth control, or breastfeeding.
My hemoglobin level is below the normal range for my gender.
I have blood in my urine that has not been explained.
I have low blood volume or chronic kidney problems.
I do not have any severe illnesses other than heart issues.
I have had diabetic retinopathy in the past.
I am on dialysis or my kidney function is low.
I am HIV or Hepatitis B/C positive.
I have had a severe diabetes complication needing treatment in the last 3 months.
I am unable to understand and give consent for treatment.
I have painful gallstones.
I have a history of diabetes insipidus.
I have a cancer other than in situ or basal cell skin cancer.
I have had a heart event or procedure in the last 3 months or have congestive heart failure.
I have a history of Addison's disease or chronic adrenal insufficiency.
I have had medullary thyroid cancer or MEN 2 syndrome.
I have had repeated yeast infections in the genital area.
Treatment Details
The trial is testing if adding dapagliflozin to semaglutide and insulin (triple therapy) better controls blood sugar in Type 1 Diabetes than just semaglutide and insulin (dual therapy) or insulin alone. Participants will receive one of these combinations to compare effectiveness.
4Treatment groups
Experimental Treatment
Active Control
Placebo Group
Group I: Triple therapyExperimental Treatment3 Interventions
Once a day oral pill (green, plain, diamond shaped film coated 5 mg tablet) of Dapagliflozin (an SGLT-2 inhibitor) added to once a week injection of semaglutide and standard of care insulin in the second 6 months of 1/2 of the dual therapy arm (1/3 of total patients (38 patients)). Dapagliflozin will be started at 5 mg for one week, and then increased to 10 mg for the remainder of the study
Group II: Dual TherapyExperimental Treatment2 Interventions
Once a week injection of Semaglutide (a GLP-1 receptor agonist) in addition to standard of care insulin for the first six months in 2/3 of patients (76 patients). Semaglutide is a clear, colorless solution that contains 2 mg of semaglutide in a 1.5 mL (1.34 mg/mL) pre-filled, disposable, single-patient-use pen injector. Semaglutide will be started at the 0.25 mg dose for the first two weeks, then increased to 0.5 mg at week 2, and then yet again increased to 1.0 mg at week 4.
Group III: ControlActive Control1 Intervention
Standard of care insulin will be used as an active comparator arm for 1/3 of patients (38 patients) for the entire duration of the study.
Group IV: Triple therapy controlPlacebo Group3 Interventions
Once a day oral pill (green, plain, diamond shaped film coated 5 mg tablet) of the Placebo form of Dapagliflozin added to once a week injection of semaglutide and standard of care insulin in the second 6 months of 1/2 of the dual therapy arm (1/3 of total patients (38 patients)).
Insulin is already approved in European Union, United States, Canada for the following indications:
🇪🇺 Approved in European Union as Insulin for:
- Diabetes mellitus
🇺🇸 Approved in United States as Insulin for:
- Diabetes mellitus
🇨🇦 Approved in Canada as Insulin for:
- Diabetes mellitus
Find a clinic near you
Research locations nearbySelect from list below to view details:
Diabetes and Endocrinology Research Center of WNYWilliamsville, NY
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Who is running the clinical trial?
State University of New York at BuffaloLead Sponsor
University of GlasgowCollaborator
Juvenile Diabetes Research FoundationCollaborator
References
[Use of human insulin preparations in the treatment of patients with insulin-dependent diabetes mellitus]. [2016]The authors presented the results of a study of human insulin drugs Monotard HM and Actrapid HM (Novo, Denmark) for type I diabetes mellitus. They stressed their efficacy in therapy of insulin dependent diabetes mellitus: a course of disease became less labile, the time of achieving compensation was reduced; the drugs proved to be effective in the treatment of post-injection insulinlipodystrophies, in body mass deficiency; a tendency to a decrease in daily insulin requirement, serum insulin binding capacity, and in increase in the content of free insulin were noted.
[The insulin analog, Humalog, in discontinuous: from pharmacology to clinical use]. [2011]Humalog is the first analog of human insulin to be evaluated on a large scale in clinical conditions by discontinuous subcutaneous administration. Eight international multicentric studies have investigated the efficacy and tolerance of Humalog in protocols with 3 daily insulin injections (3 preprandial injections of Humalog associated with 1 or 2 injections of Umuline NPH or Umuline Zinc). A total of 2834 patients participated in these studies, including 2,277 who used Humalog. In addition to these trials, more than 5,000 patients had used Humalog by 1996, in some cases for more than 3 years. In insulin-dependent diabetes (IDDM), glycaemic control at the time of inclusion of patients in these protocols, as evaluated by HbA1C, was generally moderate (8 to 9%) despite 3 daily injections. This did not constitute intensive care since basal insulin for half of these patients was ensured by only a single daily injection. In these conditions, the results obtained showing significant postprandial improvement in glycaemic control and a significant reduction of the number of hypoglycaemic episodes, particularly at night, are important even though HbA1C levels were not significantly decreased. In a more recent crossover study (1996), 199 well-controlled IDDM patients (HbA1C = 7.3%) were treated intensively by multiple injections. The number of severe hypoglycaemic episodes with coma was only one-fifth that of the group treated by Humalog (equivalent to a reduction of 26 comas per 100 patients/year) in the absence of any significant modification of HbA1C. No differences were noted for lipids, adverse side effects or severe events (except hypoglycaemic episodes) and immunogenicity. In non-insulin-dependent diabetes, the results were similar but less impressive concerning the improvement in postprandial glycaemic control and the reduction in hypoglycaemic episodes. In addition to the significant results obtained in these studies, Humalog was favoured by the vast majority of patients. It is likely that Humalog will allow intensified treatment of diabetes in very favourable conditions, and that more patients will achieve the difficult goal of normalising glycaemia. However, a single injection of NPH or prolonged insulin is not sufficient for that purpose. Two daily injections will generally be necessary.
Safety of insulin lispro: pooled data from clinical trials. [2019]The safety of insulin lispro was compared with that of regular human insulin of recombinant DNA origin (Humulin R, Lilly), with special emphasis on the development and progression of the chronic complications of diabetes mellitus in relation to insulin therapy. Ten clinical trials of 3634 patients with type 1 and type 2 diabetes mellitus were analyzed. The primary focus was treatment-emergent adverse events, and the secondary focus was the development and progression of the chronic complications of diabetes. The evaluations were based on pertinent laboratory values, predetermined disease-specific COSTART (coding symbol and thesaurus for adverse event terminology) terms, physician evaluations of patients, and physical examinations. There were no clinically or statistically significant differences in the frequency of treatment-emergent adverse events or progression of retinopathy, neuropathy, or cardiovascular disease reported with each therapy. There was no difference between insulin lispro and Humulin R in the occurrence and progression of kidney disease as measured by changes in serum creatinine levels. Pooled data from clinical studies show that insulin lispro has a safety profile comparable to that of Humulin R.
Differences in bioactivity between human insulin and insulin analogues approved for therapeutic use- compilation of reports from the past 20 years. [2021]In order to provide comprehensive information on the differences in bioactivity between human insulin and insulin analogues, published in vitro comparisons of human insulin and the rapid acting analogues insulin lispro (Humalog®), insulin aspart ( NovoRapid®), insulin glulisine (Apidra®), and the slow acting analogues insulin glargine (Lantus®), and insulin detemir (Levemir®) were gathered from the past 20 years (except for receptor binding studies). A total of 50 reports were retrieved, with great heterogeneity among study methodology. However, various differences in bioactivity compared to human insulin were obvious (e.g. differences in effects on metabolism, mitogenesis, apoptosis, intracellular signalling, thrombocyte function, protein degradation). Whether or not these differences have clinical bearings (and among which patient populations) remains to be determined.
[New insulin types in type 1 diabetes mellitus]. [2015]Since its discovery almost a century ago, insulin remains the mainstay of treatment of patients with type 1 diabetes mellitus. Although progress in the synthesis of new formulations has been remarkable, the physiological profile of insulin is still different from that observed with preparations available nowadays. In the last decade, the introduction into clinical practice of insulin analogues has allowed significantly improvement in glycemic control and has facilitated the spread of basal/bolus patterns, the most physiological ones until now. Despite the benefits of basal analogues, glycemia often varies considerably when used as a single daily injection and this is why new molecules have been further investigated. Improvement has been achieved especially in terms of duration and rate of hypoglycemia, the main limiting factor of intensive therapy. This article reviews the available data concerning the new basal insulin analogues, degludec, pegylated lispro and glargine U300, and new formulations currently under development.
New Insulin Glargine 300 U/mL for the Treatment of Type 1 and Type 2 Diabetes Mellitus. [2022]To describe the studies evaluating the efficacy and safety of new insulin glargine 300 U/mL (Gla-300) as a basal insulin in the treatment of type 1 (T1DM) and type 2 (T2DM) diabetes mellitus.
Semaglutide: First Global Approval. [2019]Novo Nordisk has developed a subcutaneous formulation of semaglutide (Ozempic®), a modified human glucagon-like peptide-1 (GLP-1) analogue, for the treatment of type 2 diabetes mellitus. It has been developed using Novo Nordisk's proprietary protein-acylation technology, and is administered using an injection device. Semaglutide lowers blood glucose by stimulating the release of insulin and also lowers body weight. Once-weekly subcutaneous semaglutide has recently been approved in the US, Puerto Rico and Canada, and has received a positive opinion in the EU for the treatment of patients with type 2 diabetes. It will be launched as the Ozempic® Pen, a pre-filled device. Semaglutide is also under regulatory review in Japan and Switzerland for the treatment of type 2 diabetes. Clinical development for obesity, non-alcoholic steatohepatitis and non-alcoholic fatty liver disease is underway worldwide. This article summarizes the milestones in the development of semaglutide leading to this first approval for type 2 diabetes.
[Basal insulin analogue versus traditional NPH insulin in basal bolus therapy of children and adolescents with type 1 diabetes]. [2020]The efficacy and safety of a combination of ultrashort acting insulin aspart (Novorapid) with determir (Levemir) and glargin (Lantus) versus the traditional NPH-insulin (Protafan) used in basal bolus therapy were evaluated in 112 children and adolescents with type 1 diabetes 12 and 24 weeks after treatment. According to the type of basal insulin, the patients were divided into 3 groups. A significant decrease in HbA1c levels was revealed in the group of detemir-treated patients. The analogues of basal insulin significantly reduced the risk of hypoglycemias, by simultaneously improving the quality of glycemia control. Their use could cause a significant decrease in the fasting plasma level of glucose, by completely refusing 6.00 extra insulin doses. In the detemir group, the daily dose was increased, by lowering the amount of basal insulin. The dose of dietary insulin underwent changes in the glargin group. Body mass index remained unchanged in the detemir group over 24 weeks of treatment.
Treatment Patterns and Outcomes, Before and After Humulin R U-500 Initiation, Among High-Dose Type 2 Diabetes Mellitus Patients in the United States. [2022]Severely insulin-resistant type 2 diabetes (T2D) patients face unique treatment challenges. Humulin R U-500 (U-500R) as insulin monotherapy with both basal/bolus properties addresses these challenges, although it remains understudied. This retrospective study compared real-world patient characteristics, treatment patterns, and outcomes before and after U-500R initiation.
A randomized pharmacokinetic and pharmacodynamic trial of two regular human insulins demonstrates bioequivalence in type 1 diabetes and availability of biosimilar insulin may improve access to this medication. [2023]To compare the pharmacokinetic (PK) and pharmacodynamic (PD) effects and safety of therapeutic dosages of a regular insulin (experimental drug) produced by Bioton S.A. (Warsaw, Poland) versus Humulin® R, a regular insulin (reference drug) produced by Eli Lilly (Indianapolis, Indiana).