The Future of Basal Insulin

Shah, Viral N.; Moser, Emily; Blau, Aaron; Dhingra, Megha; Garg, Satish K.

doi:10.1089/dia.2013.0228

Cited by 25 publications

(26 citation statements)

References 58 publications

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“…The utilization of therapeutic accumulation results in a flat pharmacokinetics (PK) profile at steady state with a peak‐to‐trough ratio of ~1.5, which clinically translates into low day‐to‐day variability in both PK and pharmacodynamics (PD) . Figure shows the flat and less‐variable PD activity profile desirable for a basal insulin, observed when BIL was compared with glargine at steady state in euglycaemic clamps repeated on three separate days in patients with T1D…”

Section: Receptor Binding Pharmacology and Mechanism Of Action Of Bilmentioning

confidence: 99%

Basal insulin peglispro: Overview of a novel long‐acting insulin with reduced peripheral effect resulting in a hepato‐preferential action

Jacober

Prince

Beals

et al. 2016

Diabetes Obesity Metabolism

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).Basal insulin peglispro (BIL) is a novel basal insulin with a flat, prolonged activity profile. BIL has been demonstrated in a dog model, in healthy men and in patients with type 1 diabetes (T1D) to have significant hepato-preferential action resulting from reduced peripheral activity. In the IMAGINE-Phase 3 clinical trial program, more than 6000 patients were included, of whom 3900 received BIL. Of the 7 pivotal IMAGINE trials, 3 studies were double-blinded and 3 were in T1D patients. BIL consistently demonstrated a greater HbA1c reduction, less glycaemic variability and a clinically relevant reduction in the rates of nocturnal hypoglycaemia across comparator [glargine and isophane insulin (NPH)] studies. Trials using basal/bolus regimens had higher rates of total hypoglycaemia with BIL due to higher rates of daytime hypoglycaemia.Severe hypoglycaemia rates were similar to comparator among both patients with T1D or type 2 diabetes (T2D). T1D patients lost weight compared with glargine (GL). Patients with T2D tended to gain less weight with BIL than with glargine. Compared to glargine, BIL was associated with higher liver fat, triglycerides and alanine aminotransferase (ALT) levels, including a higher frequency of elevation of ALT ≥3 times the upper limit of normal, but without severe, acute drug-induced liver injury. Injection site reactions, primarily lipohypertrophy, were more frequent with BIL. In conclusion, BIL demonstrated better glycaemic control with reduced glucose variability and nocturnal hypoglycaemia but higher triglycerides, ALT and liver fat relative to conventional comparator insulin. The hepato-preferential action of BIL with reduced peripheral activity may account for these findings. K E Y W O R D Sbasal insulin, drug development, drug mechanism, hypoglycaemia, insulin therapy Insulin therapy has long been a mainstay of therapy for type 1 and

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Section: Receptor Binding Pharmacology and Mechanism Of Action Of Bilmentioning

confidence: 99%

Basal insulin peglispro: Overview of a novel long‐acting insulin with reduced peripheral effect resulting in a hepato‐preferential action

Jacober

Prince

Beals

et al. 2016

Diabetes Obesity Metabolism

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“…Because the early short-acting insulins were derived from bovine and porcine pancreata, they were limited by requiring multiple daily injections, immunological reactions, lipodystrophy, and unpredictable hypoglycemic and hyperglycemic events. 15 Early developments focused on insulin purification, different formulations, and prolonging the duration of action. With the introduction of long-acting insulins in the 1930-1940s (protamine zinc insulin and NPH), patients were able to take one or two injections of long-acting insulin and three or more injections of short-acting insulin a day for optimal glycemic control.…”

Section: History Of the Artificial Pancreas (Cl System)mentioning

confidence: 99%

“…With the introduction of long-acting insulins in the 1930-1940s (protamine zinc insulin and NPH), patients were able to take one or two injections of long-acting insulin and three or more injections of short-acting insulin a day for optimal glycemic control. 15 The DCCT established the usefulness of IIT (MDI or CSII) in the management of diabetes. 3 However, early insulins used in the DCCT were limited by marked inter-and intra-individual variability and nocturnal hypoglycemia as a result of peak action at 4-6 h, which made it difficult to achieve desired glucose control.…”

Section: History Of the Artificial Pancreas (Cl System)mentioning

confidence: 99%

“…The currently available rapid-acting (insulin lispro, insulin glulisine, insulin aspart) and long-acting (insulin glargine, insulin detemir) insulin analogs have better pharmacokinetics and pharmacodynamics properties than earlier insulins and have been shown to reduce the occurrence of hypoglycemic events while maintaining or improving glycemic control. 15 The first insulin pump developed by Kadish 16 in 1964 was large in size and included an autoanalyzer to measure blood glucose. However, it was impractical to use this device and did not receive much attention.…”

Section: History Of the Artificial Pancreas (Cl System)mentioning

confidence: 99%

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Closed-Loop System in the Management of Diabetes: Past, Present, and Future

Shah

Shoskes

Tawfik

et al. 2014

Diabetes Technology & Therapeutics

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Intensive insulin therapy (IIT) has been shown to reduce micro- and macrovascular complications in patients with type 1 diabetes mellitus (T1DM). However, IIT is associated with a significant increase in severe hypoglycemic events, resulting in increased morbidity and mortality. Optimization of glycemic control without hypoglycemia (especially nocturnal) should be the next major goal for subjects on insulin treatment. The use of insulin pumps along with continuous glucose monitors (CGMs) has made it easier but requires significant resources and patient education. Research is ongoing to close the loop by integrating the pump and the CGM using different algorithms. The currently available closed-loop system is the threshold suspend. Steps needed to achieve a near-perfect closed-loop are (1) a control-to-range system that will reduce the incidence and/or severity of hyper- and/or hypoglycemia by adjusting the insulin dose and (2) a control-to-target system, a fully automated or hybrid system that sets target glucose levels to individual needs and maintains glucose levels throughout the day using insulin (unihormonal) alone or with other hormones such as glucagon or possibly pramlintide (bihormonal). Future research is also focusing on better insulin delivery devices (pumps), more accurate CGMs, better predictive algorithms, and ultra-rapid-acting insulin analogs to make the closed-loop system as physiological as possible.

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“…Additionally, there has been a significant decline in microvascular complications. [56] As a result of this, the life expectancy in patients with T1DM has increased remarkably[7] and more patients with T1DM are now older than 60 years. Hence, there is need to focus more on other age related complications which can be potentiated by diabetes, including osteoporosis, cardiovascular disorders and cognition in older individuals with T1DM.…”

Section: Introductionmentioning

confidence: 99%

Type 1 diabetes and osteoporosis: A review of literature

Dhaon¹,

Shah²

2014

Indian J Endocr Metab

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With better care and intensive insulin therapy, microvascular complications have reduced and longevity has increased in patients with type 1 diabetes (T1DM). Therefore, there is a need to change the focus from microvascular complications to cardiovascular disease and osteoporosis. Though number of studies from other parts of the world show that patients with T1DM are at increased risk of osteoporosis and fractures, there is a paucity of data from India. A number of factors and mechanisms affecting bone health in patients with T1DM have been proposed. The main defect in genesis of osteoporosis is osteoblastic function, rather than osteoclastic overfunction. Assessment of bone mineral density by dual X-ray absorptiometry and other risk factors for osteoporosis, as a part of diagnostic procedure can help to design tailored treatment plans. A physically active healthy lifestyle, prevention of diabetic complications and adequate calcium and vitamin D supplementation are the mainstay for prevention of osteoporosis. Treatment of osteoporosis is not evidence based but it is proposed to be similar to osteoporosis associated with other conditions. Bisphosphonates are the mainstay for treatment of osteoporosis in patients with T1DM. However, more studies are needed to make definitive guidelines on prevention and treatment of osteoporosis in patients with T1DM.

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The Future of Basal Insulin

Cited by 25 publications

References 58 publications

Basal insulin peglispro: Overview of a novel long‐acting insulin with reduced peripheral effect resulting in a hepato‐preferential action

Basal insulin peglispro: Overview of a novel long‐acting insulin with reduced peripheral effect resulting in a hepato‐preferential action

Closed-Loop System in the Management of Diabetes: Past, Present, and Future

Type 1 diabetes and osteoporosis: A review of literature

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