A Mechanism-based Disease Progression Model for Comparison of Long-term Effects of Pioglitazone, Metformin and Gliclazide on Disease Processes Underlying Type 2 Diabetes Mellitus

@article{Winter2006AMD,
  title={A Mechanism-based Disease Progression Model for Comparison of Long-term Effects of Pioglitazone, Metformin and Gliclazide on Disease Processes Underlying Type 2 Diabetes Mellitus},
  author={Willem de Winter and Joost DeJongh and Teun M. Post and Bart A. Ploeger and Richard Urquhart and Ian K Moules and David J A Eckland and Meindert Danhof},
  journal={Journal of Pharmacokinetics and Pharmacodynamics},
  year={2006},
  volume={33},
  pages={313-343}
}
Effective long-term treatment of Type 2 Diabetes Mellitus (T2DM) implies modification of the disease processes that cause this progressive disorder. This paper proposes a mechanism-based approach to disease progression modeling of T2DM that aims to provide the ability to describe and quantify the effects of treatment on the time-course of the progressive loss of β-cell function and insulin-sensitivity underlying T2DM. It develops a population pharmacodynamic model that incorporates mechanism… 
Modeling disease progression in newly diagnosed type 2 diabetes
TLDR
A mechanistic model was developed to quantitatively characterize the dynamic interactions among β-cell function, plasma fasting glucose (PFG), fasting insulin (FI), and the degree of insulin resistance, starting from an early stage of T2DM and yields insights into factors that are critical for long-term glycemic control.
Evaluation of the long-term durability and glycemic control of fasting plasma glucose and glycosylated hemoglobin for pioglitazone in Japanese patients with type 2 diabetes.
TLDR
Pioglitazone was found to result in improved glycemic control and durability compared with control treatment and was superior in both time to maximum effect and the magnitude of reduction achieved in FPG and HbA1c.
Development and Qualification of a Drug‐Disease Modeling Platform to Characterize Clinically Relevant Endpoints in Type 2 Diabetes Trials
TLDR
The model was able to simultaneously characterize changes in fasting plasma glucose, fasting serum insulin, and glycated hemoglobin A1c following administration of sulfonylurea, metformin, and thiazolidinedione as well as disease progression in clinical trials ranging from 16–104 weeks of treatment.
Efficacy and Tolerability of Pioglitazone in Patients with Type 2 Diabetes Mellitus
TLDR
In conclusion, pioglitazone is an effective oral antihyperglycaemic agent with additional cardiovascular and lipid benefits that allows for the successful management of patients with T2DM.
A Model for Glucose, Insulin, and Beta‐Cell Dynamics in Subjects With Insulin Resistance and Patients With Type 2 Diabetes
TLDR
A semi‐mechanistic PKPD model incorporating fasting plasma glucose, fasting insulin, insulin sensitivity, and BCM in patients at various disease stages was developed and well described the heterogeneous populations, ranging from nondiabetic, insulin‐resistant subjects to long‐term treated T2DM patients.
Effects of IL-1β–Blocking Therapies in Type 2 Diabetes Mellitus: A Quantitative Systems Pharmacology Modeling Approach to Explore Underlying Mechanisms
TLDR
It is proposed that improved β‐cell function, rather than mass, is likely to explain the main IL‐1β–blocking effects seen in current clinical data, but that improvedβ‐cell mass might result in disease‐modifying effects not clearly distinguishable until >1 year after treatment.
A Comprehensive Review of Novel Drug–Disease Models in Diabetes Drug Development
TLDR
A comprehensive overview of the quantitative approaches that have been reported since the 2008 review by Landersdorfer and Jusko in an increasing order of complexity, starting with glucose homeostasis models is provided.
Modeling glucose-insulin kinetics and development of type 2 diabetes in offspring of diabetic parents
TLDR
The central hypothesis is that the development of T2D can be described and characterized by the glucose-insulin kinetics by employing a population-PK/PD based disease development analysis.
Mechanism-based disease progression modeling of type 2 diabetes in Goto-Kakizaki rats
TLDR
The diabetes model quantitatively described the glucose/insulin inter-regulation and HbA1c production and reflected the underlying pathogenic factors of T2D—IR and β-cell dysfunction and could be extended to incorporate other biomarkers and effects of various anti-diabetic drugs.
Weight‐HbA1c‐insulin‐glucose model for describing disease progression of type 2 diabetes
TLDR
Weight change as an effector on insulin sensitivity was successfully evaluated in a semi‐mechanistic population model to describe the disease progression of type 2 diabetic mellitus.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 31 REFERENCES
Population PKPD modelling of the long-term hypoglycaemic effect of gliclazide given as a once-a-day modified release (MR) formulation.
TLDR
This population PKPD analysis has characterized the relationship between the exposure to gliclazide and its long-term hypoglycaemic effect, and has established that the intersubject variability in response is mostly related to disease state.
Efficacy and safety of pioglitazone versus metformin in patients with type 2 diabetes mellitus: a double-blind, randomized trial.
TLDR
HbA1c reduction is similar after pioglitazone and metformin monotherapies, but differences in FPG, plasma lipids, and adverse effects between the two compounds may influence decision-making in individual prescribers.
Pathophysiology and pharmacological treatment of insulin resistance.
TLDR
This review focuses on the pathophysiology and molecular pathogenesis of insulin resistance and on the capability of antihyperglycemic pharmacological agents to treat insulin resistance, i.e., a-glucosidase inhibitors, biguanides, thiazolidinediones, sulfonylureas, and insulin.
Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34)
TLDR
Since intensive glucose control with metformin appears to decrease the risk of diabetes-related endpoints in overweight diabetic patients, and is associated with less weight gain and fewer hypoglycaemic attacks than are insulin and sulphonylureas, it may be the first-line pharmacological therapy of choice in these patients.
Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group.
TLDR
The effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a randomised controlled trial were compared.
Comparison of pioglitazone and gliclazide in sustaining glycemic control over 2 years in patients with type 2 diabetes.
TLDR
Compared with gliclazide treatment, pioglitazone treatment produced a larger decrease in HbA(1c), a larger increase in HOMA-%S, and a smaller increase inHOMa-%B during the 2nd year of treatment.
Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group.
TLDR
Metformin monotherapy and combination therapy with metformin and sulfonylurea are well tolerated and improve glycemic control and lipid concentrations in patients with NIDDM whose diabetes is poorly controlled with diet or sulfonyLurea therapy alone.
Pioglitazone hydrochloride monotherapy improves glycemic control in the treatment of patients with type 2 diabetes: a 6-month randomized placebo-controlled dose-response study. The Pioglitazone 001 Study Group.
TLDR
Pioglitazone monotherapy significantly improves HbA1c and FPG while producing beneficial effects on serum lipids in patients with type 2 diabetes with no evidence of drug-induced hepatotoxicity.
Oral antihyperglycemic therapy for type 2 diabetes: scientific review.
TLDR
With few exceptions, the available oral antidiabetic agents are equally effective at lowering glucose concentrations and their mechanisms of action are different, however, and as a result they appear to have distinct metabolic effects.
Use and abuse of HOMA modeling.
TLDR
The HOMA model has become a widely used clinical and epidemiological tool and, when used appropriately, it can yield valuable data, however, as with all models, the primary input data needs to be robust, and the data need to be interpreted carefully.
...
1
2
3
4
...