- |||||||||| Symlin (pramlintide) / AstraZeneca, Tresiba (insulin degludec) / Novo Nordisk, NovoLog (insulin aspart) / Novo Nordisk
[VIRTUAL] ADO09, a Coformulation of Pramlintide (PRAM) and Insulin A21G, Improves Postprandial Glucose vs. Novolog in Type 1 Diabetes (T1D) () - May 18, 2020 - Abstract #ADA2020ADA_3011;
On the last outpatient day, mean daily bolus doses were 4 U lower with ADO09 (-21%, p=0.05). Both treatments were well tolerated with more gastrointestinal adverse events (24 vs. 6) observed with ADO09, consistent with typical effect of PRAM.In conclusion, ADO09 significantly improved CGM metrics including TIR, weight control and bolus insulin needs vs. Novolog over 24 days of use.
- |||||||||| metformin / Generic mfg.
Journal: Non-insulin treatments for Type 1 diabetes: critical appraisal of the available evidence and insight into future directions. (Pubmed Central) - Mar 29, 2020
The evaluation of new therapies, effective in Type 2 diabetes, as adjuncts to insulin therapy represents a promising strategy, particularly given the beneficial effects on cardiovascular and renal outcomes in people with Type 2 diabetes with or at high risk of complications that are also observed in patients with Type 1 diabetes. As the population with Type 1 diabetes ages, our mission is to evolve and provide better tools and improved therapies to excel, not only in glycaemic control but also in risk reduction and reduction of complications.
- |||||||||| Byetta (exenatide) / AstraZeneca
Journal: Glucagon-like peptide 1 receptor agonists in type 1 diabetes mellitus. (Pubmed Central) - Mar 3, 2020
Patients who have detectable C-peptide and/or are overweight or cannot achieve glycemic goals without hypoglycemia have been found to benefit the most from GLP-1 RA therapy. Further studies are warranted to evaluate these agents' potential impact on clinical outcomes such as microvascular and macrovascular complications.
- |||||||||| Symlin (pramlintide) / AstraZeneca
Journal: Human Amylin: From Pathology to Physiology and Pharmacology. (Pubmed Central) - Feb 9, 2020
The history of amylin's discovery is a representative example of how a pathological finding can translate into physiological exploration and lead to pharmacological intervention. Understanding the importance of transitioning from pathology to physiology and pharmacology can provide novel insight into diabetes mellitus and Alzheimer's disease.
- |||||||||| Symlin (pramlintide) / AstraZeneca
BIOMIMETIC INSULIN-PRAMLINTIDE CO-FORMULATION ENABLED BY SUPRAMOLECULAR PEGYLATION (E-Poster Area) - Dec 29, 2019 - Abstract #ATTD2020ATTD_601;
Using diabetic rat and pig models, we demonstrate that co-formulation with CB[7]-PEG modifies the pharmacokinetics of both insulin and pramlintide, increasing the overlap between the time-frame of action of the two hormones, thus mimicking endogenous secretion and restoring meal-time glucagon suppression. Conclusions This insulin-pramlintide co-formulation more closely mimics endogenous co-secretion of insulin and amylin from the beta-cells and shows promise as a single administration therapy that could reduce patient burden and enhance diabetes management.
- |||||||||| metformin / Generic mfg., Jardiance (empagliflozin) / Eli Lilly, Boehringer Ingelheim, Farxiga (dapagliflozin) / Ono Pharma, AstraZeneca
SGLT inhibitors for type 1 diabetes - Introduction (Auditorium A) - Dec 29, 2019 - Abstract #ATTD2020ATTD_108;
Several molecules (like metformin, GLP analogs, coleselvelam, and DPP-4 inhibitors) have been evaluated as adjunctive therapeutic options for T1D[2],[3]...The only FDA-approved option for adjunctive therapy for patients with T1D is pramlintide, which is rarely used because of GI side-effects and risk of severe hypoglycemia[4]...The second trial (replicating real-life use) using a dual SGLT 1 and 2 inhibitor (inTandem 3-Sotagliflozin in T1D)[3] showed significant reduction in A1c, hypoglycemia, especially severe (<55mg/dL) and weight loss...Lastly, EASE 2 and 3 trials[2] using Empagliflozin in T1D and showed similar benefits and risks like Dapa and Sota except the authors recommended a smaller dose of 2.5mg a day to be considered for T1D (due to no increase in DKA risk, but efficacy on A1c was about 50%) based on a small sample size in EASE 3.Results More recently, a meta-analysis of inTandem studies showed significant reduction in hypoglycemia (<70mg/dL) and severe hypoglycemia (defined as <54mg/dL)[1]...In the USA, no SGLT inhibitor has been approved for patients with T1D and the FDA has issued a complete response letter (CRL) for both sota- and dapagliflozin. If and when these drugs are approved for patients with T1D in the USA, the risk of DKA will need to be mitigated by proper education for patients and providers following the STICH and STOP DKA protocols[2],[3],[4].Conclusions Finally, the use of SGLT inhibitors as adjunctive therapy for T1D may allow many more patients to achieve target A1cs without any further weight gain and may in fact have long-term cardiovascular and renal benefits as have been shown in patients with T2D.
- |||||||||| metformin / Generic mfg., Symlin (pramlintide) / AstraZeneca
Pramlintide and Metformin in type 1 diabetes (Rome) - Dec 29, 2019 - Abstract #ATTD2020ATTD_77;
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. Results / Part 3 Not Relevant Conclusions / Part 4 Not Relevant
- |||||||||| Lantus (insulin glargine) / Sanofi
Journal: Physico-chemical stability of co-formulation of PEGylated human amylin with insulin. (Pubmed Central) - Dec 26, 2019
When hAmy-PEG5k (100 or 500 µg/mL) was added to the commercial formulations of either insulin glargine or detemir (95 IU/mL), the combinations remained stable after 6 months stored at 4 °C, as probed by ThT, dynamic light scattering (DLS) measurements and high performance liquid chromatography (HPLC) analyses, confirming the absence of amyloid fibers, minor aggregation products or loss of material. These results suggest hAmy-PEG5k and the insulin analogs glargine and detemir are physicochemically compatible and are candidate ready-to-use fixed-dose combinations.
- |||||||||| Review, Journal: Drugs for type 2 diabetes. (Pubmed Central) - Dec 22, 2019
These results suggest hAmy-PEG5k and the insulin analogs glargine and detemir are physicochemically compatible and are candidate ready-to-use fixed-dose combinations. No abstract available
- |||||||||| Symlin (pramlintide) / AstraZeneca, taspoglutide (ITM-077) / Teijin, taspoglutide (BIM51077) / Roche
Journal: PEGylated prodrugs of antidiabetic peptides amylin and GLP-1. (Pubmed Central) - Oct 27, 2019
Thus, taspoglutide was released even after an incubation period of 24 h in serum with the content of degraded taspoglutide being below 2% in the prodrug at this time point. This PEG-prodrug technology could provide precisely tuned long-acting anti-diabetic and anti-obesity therapies and even once-monthly administration intervals when combined with other formulation strategies.
- |||||||||| Symlin (pramlintide) / AstraZeneca
Enrollment closed, Trial completion date, Trial primary completion date, Head-to-Head: Amylin and CGRP Head to Head Provocation in Migraine Without Aura Patients (clinicaltrials.gov) - Sep 26, 2019
P=N/A, N=34, Active, not recruiting,
This PEG-prodrug technology could provide precisely tuned long-acting anti-diabetic and anti-obesity therapies and even once-monthly administration intervals when combined with other formulation strategies. Recruiting --> Active, not recruiting | Trial completion date: Jul 2019 --> Sep 2019 | Trial primary completion date: Jul 2019 --> Sep 2019
- |||||||||| Symlin (pramlintide) / AstraZeneca
Journal: Neuroprotective Effects of Amylin Analogues on Alzheimer's Disease Pathogenesis and Cognition. (Pubmed Central) - Sep 20, 2019
Pramlintide, a synthetic analogue of the pancreatic hormone amylin, has been developed and used for years now as a treatment for both type I diabetes and T2D due to the loss of β-islet cells responsible for producing amylin...This review aims at addressing parallels between T2D and AD at a pathological and functional level, focusing on amylin signaling as a key, overlapping mediator in both diseases. The potential therapeutic use of this hormone to treat AD will also be explored from a mechanistic viewpoint.
- |||||||||| Symlin (pramlintide) / AstraZeneca
Review, Journal: IAPP and type 1 diabetes: implications for immunity, metabolism and islet transplants. (Pubmed Central) - Sep 16, 2019
Pramlintide limits postprandial hyperglycemia by delaying gastric emptying and suppressing hyperglucagonemia, underlining the possible role of IAPP in postprandial glucose metabolism. Here, we review IAPP in the context of type 1 diabetes: from its potential involvement in type 1 diabetes pathogenesis, through its role in glucose metabolism and use of IAPP analogues as therapeutics, to its potential role in clinical islet transplant failure and considerations in this regard for future beta cell replacement strategies.
- |||||||||| Symlin (pramlintide) / AstraZeneca
Journal: Amylin Signaling in Diabetes and Alzheimer's Disease: Therapy or Pathology? (Pubmed Central) - Sep 13, 2019
The pancreatic hormone amylin has arisen as a crucial component of the disease etiology of both T2D and AD, though the exact role that amylin plays in these diseases is not yet well understood. Here, we critically review the current literature that utilizes human amylin or its synthetic analogue, pramlintide, as well as amylin receptor antagonists for the treatment of AD.
- |||||||||| metformin / generics
Clinical, Review, Journal: Adjuvant Pharmacotherapies to Insulin for the Treatment of Type 1 Diabetes. (Pubmed Central) - Aug 30, 2019
Sodium-glucose cotransporter (SGLT)-2 inhibitors, dual SGLT-1/2 inhibitors, and pramlintide have been shown to reduce hemoglobin A1c, induce weight loss, and lower insulin dose...Although not devoid of side effects, additive pharmacotherapies in T1D can improve glycemic control and lower body weight and insulin requirement. Longer studies are needed before consideration for widespread clinical care.
- |||||||||| Jardiance (empagliflozin) / Eli Lilly, Boehringer Ingelheim, Farxiga (dapagliflozin) / Ono Pharma, AstraZeneca
Speaker (Auditorium) - Aug 15, 2019 - Abstract #IDF2019IDF_28;
If and when these drugs are approved for patients with T1D in the USA, the risk of DKA will need to be mitigated by proper education for patients and providers following the STICH and STOP DKA protocols , , . Finally, the use of SGLT inhibitors as adjunctive therapy for T1D may allow many more patients to achieve target A1cs without any further weight gain and may in fact have long-term cardiovascular and renal benefits as have been shown in patients with T2D.
- |||||||||| Symlin (pramlintide) / AstraZeneca
Trial completion date, Trial primary completion date, MRI: A Study of the Functional Magnetic Resonance Imaging Response to Leptin and Pramlintide (clinicaltrials.gov) - Aug 7, 2019
P=N/A, N=10, Active, not recruiting,
Finally, the use of SGLT inhibitors as adjunctive therapy for T1D may allow many more patients to achieve target A1cs without any further weight gain and may in fact have long-term cardiovascular and renal benefits as have been shown in patients with T2D. Trial completion date: Jul 2012 --> Jul 2020 | Trial primary completion date: Jul 2012 --> Jul 2020
- |||||||||| Symlin (pramlintide) / AstraZeneca, Contrave (naltrexone + bupropion) / Orexigen
Journal, Combination therapy: Combination Therapies for Obesity. (Pubmed Central) - Jun 28, 2019
A first trial has provided promising results with combination of IGB plus the GLP-1 analog, liraglutide, compared to the balloon alone. Thus, combination therapies for the treatment of obesity hold promise for introduction into clinical practice.
- |||||||||| metformin / generics
Journal: Pharmacologic Treatment Options for Type 1 Diabetes: What's New? (Pubmed Central) - May 17, 2019
Adjunctive therapies, likewise, may also overcome some of the abnormal physiology that is a hallmark of T1D. Therefore, individualized consideration of the efficacy of these agents must be measured alongside the potential adverse effects when choosing an adjunctive therapy.
- |||||||||| Symlin (pramlintide) / AstraZeneca
Trial completion date, Trial suspension, Trial primary completion date: Glucagon Counterregulation in Type 1 Diabetes (clinicaltrials.gov) - Mar 25, 2019
P=N/A, N=13, Suspended,
The LC-MS m/z values and fragmentation patterns of 4 impurities matched with the predicted degradation products of pramlintide acetate. Trial completion date: Nov 2018 --> Nov 2019 | Recruiting --> Suspended | Trial primary completion date: Oct 2018 --> Nov 2019
- |||||||||| Review, Journal: Future Pharmacotherapy for Obesity: New Anti-obesity Drugs on the Horizon. (Pubmed Central) - Oct 4, 2018
This review focuses on anti-obesity drugs in the pipeline including centrally acting agents (setmelanotide, neuropeptide Y antagonist [velneperit], zonisamide-bupropion [Empatic], cannabinoid type-1 receptor blockers), gut hormones and incretin targets (new glucagon-like-peptide-1 [GLP-1] analogues [semaglutide and oral equivalents], amylin mimetics [davalintide, dual amylin and calcitonin receptor agonists], dual action GLP-1/glucagon receptor agonists [oxyntomodulin], triple agonists [tri-agonist 1706], peptide YY, leptin analogues [combination pramlintide-metreleptin]), and other novel targets (methionine aminopeptidase 2 inhibitor [beloranib], lipase inhibitor [cetilistat], triple monoamine reuptake inhibitor [tesofensine], fibroblast growth factor 21), including anti-obesity vaccines (ghrelin, somatostatin, adenovirus36). With these new drugs in development, anti-obesity therapeutics have potential to vastly expand allowing better treatment options and personalized approach to obesity care.
- |||||||||| Symlin (pramlintide) / AstraZeneca
Enrollment open: DTAD: Multi-Center Development of a Novel Diagnostic Test for Alzheimer's Disease (clinicaltrials.gov) - Aug 16, 2018
P1, N=240, Enrolling by invitation,
With these new drugs in development, anti-obesity therapeutics have potential to vastly expand allowing better treatment options and personalized approach to obesity care. Not yet recruiting --> Enrolling by invitation
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