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Matthew C Riddle

Publications and source records attributed to Matthew C Riddle.

18 recordsLinked to original sources
PubMed2005

Making the transition from oral to insulin therapy.

The typically long delay in starting insulin for patients with type 2 diabetes mellitus may be due in part to uncertainty about how best to make the transition from oral therapy to insulin. Recent studies show that when appropriate glycemic targets are sought, with systematic titration of insulin dosage, several methods of beginning insulin may be successful. Notably, either starting with a single injection of basal insulin or starting with 3 injections of short-acting insulin at mealtimes can be effective. Studies also suggest that continuing oral therapies and using insulin analogues rather than human insulins may improve the effectiveness of insulin treatment relative to the rate of hypoglycemia and gain of weight typically seen in this setting. Starting with a single injection of insulin to control basal glycemia while continuing oral therapy is the simplest approach, and lends itself to stepwise addition of mealtime injections as needed to bring most patients to glycemic targets in a logical and practical way. Future studies should consider not only the ability of regimens to reach hemoglobin A(1c) targets but also the burden of adverse effects accompanying this effort with a given method.

Administration, Oral↗
PubMed2005

Glycemic management of type 2 diabetes: an emerging strategy with oral agents, insulins, and combinations.

The many antihyperglycemic preparations are best used for type 2 diabetes in a logical sequence, using combinations of agents, with clear targets for glycemic control. On the basis of long familiarity, proven benefit and known side effects, and low cost, the sulfonylureas, metformin, and insulin still deserve to be the standard treatments. As shown in the central shaded area of Fig. 4, standard treatment begins with monotherapy and progresses to oral combination therapy and then to two oral agents plus basal insulin. Several triggers for deviation from the standard methods are identified (see Fig. 4). The incidence of each of the conditions that require early individualized treatment has not been studied, but it seems reasonable to estimate no more than 10% each for a strongly symptomatic presentation, inability to use a sulfonylurea or metformin, inability to use insulin, or an early need for prandial therapy. If this estimate is correct, approximately two thirds of patients who are diagnosed with type 2 diabetes should do well with standard therapy for up to 10 years using the standard methods shown. Eventually, many more will need individualized treatment to maintain glycemic control. This scheme is certain to evolve as further information on the nonglycemic benefits (or hazards) of the various therapies appears and as new treatments are released. Notably, agents that mimic or potentiate the effects of gastrointestinal peptides, such as amylin and GLP- 1 analogues and dipeptidyl peptidase IV inhibitors, are likely to alter the current algorithm. For now, systematic application of the scheme (see Fig. 4) should improve the success of treatment greatly from its currently disappointing level.

Delayed-Action Preparations↗
PubMed2005

Comparison of basal insulin added to oral agents versus twice-daily premixed insulin as initial insulin therapy for type 2 diabetes.

OBJECTIVE: To compare the efficacy and safety of adding once-daily basal insulin versus switching to twice-daily premixed insulin in type 2 diabetic patients insufficiently controlled by oral antidiabetic agents (OADs). RESEARCH DESIGN AND METHODS: In a 24-week, multinational, multicenter, open, parallel group clinical trial, 371 insulin-naive patients with poor glycemic control (fasting blood glucose [FBG] >/=120 mg/dl, HbA(1c) 7.5-10.5%) on OADs (sulfonylurea plus metformin) were randomized to once-daily morning insulin glargine plus glimepiride and metformin (glargine plus OAD) or to 30% regular/70% human NPH insulin (70/30) twice daily without OADs. Insulin dosage was titrated to target FBG </=100 mg/dl (both insulins) and predinner blood glucose </=100 mg/dl (70/30 only) using a weekly forced-titration algorithm. RESULTS: Mean HbA(1c) decrease from baseline was significantly more pronounced (-1.64 vs. -1.31%, P = 0.0003), and more patients reached HbA(1c) </=7.0% without confirmed nocturnal hypoglycemia (45.5 vs. 28.6%, P = 0.0013) with glargine plus OAD than with 70/30. Similarly, FBG decrease was greater with glargine plus OAD (adjusted mean difference -17 mg/dl [-0.9 mmol/l], P < 0.0001), and more patients reached target FBG </=100 mg/dl with glargine plus OAD than with 70/30 (31.6 vs. 15.0%, P = 0.0001). Glargine plus OAD patients had fewer confirmed hypoglycemic episodes than 70/30 patients (mean 4.07 vs. 9.87/patient-year, P < 0.0001). CONCLUSIONS: Initiating insulin treatment by adding basal insulin glargine once daily to glimepiride plus metformin treatment was safer and more effective than beginning twice-daily injections of 70/30 and discontinuing OADs in type 2 diabetic patients inadequately controlled with OADs.

Adult↗
PubMed2005

Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea.

OBJECTIVE: This study evaluated the effects of exenatide, a novel incretin mimetic, in hyperglycemic patients with type 2 diabetes unable to achieve glycemic control with metformin-sulfonylurea combination therapy. RESEARCH DESIGN AND METHODS: A 30-week, double-blind, placebo-controlled study was performed in 733 subjects (aged 55 +/- 10 years, BMI 33.6 +/- 5.7 kg/m(2), A1C 8.5 +/- 1.0%; means +/- SD) randomized to 5 microg subcutaneous exenatide b.i.d. (arms A and B) or placebo for 4 weeks. Thereafter, arm A remained at 5 microg b.i.d. and arm B escalated to 10 microg b.i.d. Subjects continued taking their dose of metformin and were randomized to either maximally effective (MAX) or minimum recommended (MIN) doses of sulfonylurea. RESULTS: Week 30 A1C changes from baseline (+/-SE) were -0.8 +/- 0.1% (10 microg), -0.6 +/- 0.1% (5 microg), and +0.2 +/- 0.1% (placebo; adjusted P < 0.0001 vs. placebo), yielding placebo-adjusted reductions of -1.0% (10 microg) and -0.8% (5 microg). In the evaluable population, exenatide-treated subjects were more likely to achieve A1C < or =7% than placebo-treated subjects (34% [10 microg], 27% [5 microg], and 9% [placebo]; P < 0.0001). Both exenatide arms demonstrated significant weight loss (-1.6 +/- 0.2 kg from baseline each exenatide arm, -0.9 +/- 0.2 kg placebo; P < or = 0.01 vs. placebo). Mild or moderate nausea was the most frequent adverse event. The incidence of mild/moderate hypoglycemia was 28% (10 microg), 19% (5 microg), and 13% (placebo) and appeared lower with MIN than with MAX sulfonylurea treatment. CONCLUSIONS: Exenatide significantly reduced A1C in patients with type 2 diabetes unable to achieve adequate glycemic control with maximally effective doses of combined metformin-sulfonylurea therapy. This improvement in glycemic control was associated with no weight gain and was generally well tolerated.

Adult↗
PubMed2004

Timely initiation of basal insulin.

Recognition of the basal and postprandial components of hyperglycemia, in tandem with the development of new insulins and other clinical research, has led to a reassessment of type 2 diabetes mellitus treatment. In the future, insulin will be used earlier, treatment will intensify as the disease progresses, and combination therapy will be routine. Hyperglycemia can be controlled initially with sulfonylureas and metformin, agents that mainly improve control of fasting and preprandial glucose. When glycemic control can no longer be achieved with these and other oral agents alone, insulin treatment can be started as a single injection of a long-acting insulin. This method of supplementing basal insulin is safe, simple, and less likely to cause weight gain than multiple daily injections with shorter-acting insulins. Continuing oral agents during basal insulin therapy can provide a smoother transition to insulin and reduce the risk of loss of glycemic control. Of currently available insulins, glargine has the activity profile best suited to basal insulin therapy, with no prominent activity peak and a long duration of action, allowing a single daily injection in most cases. Although the traditional approach has been to introduce insulin therapy only after very high glucose values have persisted, despite prolonged use of oral agents alone, a more desirable strategy would be to prevent patients from ever experiencing the loss of glycemic control associated with hemoglobin A(1c) (HbA(1c)) elevations >7%. This goal could be achieved by diagnosing type 2 diabetes earlier in its course and by adding basal insulin to oral therapy much earlier. To maintain the recommended <7% HbA(1c) target level of control, treatments that target postprandial hyperglycemia will have to be added to basal insulin later on, as endogenous insulin continues to decline.

Diabetes Mellitus, Type 1↗
PubMed2003

The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients.

OBJECTIVE: To compare the abilities and associated hypoglycemia risks of insulin glargine and human NPH insulin added to oral therapy of type 2 diabetes to achieve 7% HbA(1c). RESEARCH DESIGN AND METHODS: In a randomized, open-label, parallel, 24-week multicenter trial, 756 overweight men and women with inadequate glycemic control (HbA(1c) >7.5%) on one or two oral agents continued prestudy oral agents and received bedtime glargine or NPH once daily, titrated using a simple algorithm seeking a target fasting plasma glucose (FPG) <or=100 mg/dl (5.5 mmol/l). Outcome measures were FPG, HbA(1c), hypoglycemia, and percentage of patients reaching HbA(1c) <or=7% without documented nocturnal hypoglycemia. RESULTS: Mean FPG at end point was similar with glargine and NPH (117 vs. 120 mg/dl [6.5 vs. 6.7 mmol/l]), as was HbA(1c) (6.96 vs. 6.97%). A majority of patients ( approximately 60%) attained HbA(1c) <or=7% with each insulin type. However, nearly 25% more patients attained this without documented nocturnal hypoglycemia (<or=72 mg/dl [4.0 mmol/l]) with glargine (33.2 vs. 26.7%, P < 0.05). Moreover, rates of other categories of symptomatic hypoglycemia were 21-48% lower with glargine. CONCLUSIONS: Systematically titrating bedtime basal insulin added to oral therapy can safely achieve 7% HbA(1c) in a majority of overweight patients with type 2 diabetes with HbA(1c) between 7.5 and 10.0% on oral agents alone. In doing this, glargine causes significantly less nocturnal hypoglycemia than NPH, thus reducing a leading barrier to initiating insulin. This simple regimen may facilitate earlier and effective insulin use in routine medical practice, improving achievement of recommended standards of diabetes care.

Administration, Oral↗
PubMed2002

Current oral agents for type 2 diabetes. Many options, but which to choose when?

Increasingly, type 2 diabetes takes a toll on public health and healthcare costs in the United States. Although the remedy for this growing problem is very complex, two critical components of its control are prevention and effective therapy. Progress in diabetes prevention is likely to take decades. But fortunately, growth in our understanding of what occurs in this chronic disease has led to advances in the pharmacologic options aimed at decreasing hyperglycemia, the main clinically measurable metabolic consequence of diabetes. In this article, Drs Ahmann and Riddle provide an overview of the oral agents now available for the treatment of diabetes and discuss the clinical factors that help determine when to use which medication and what outcome to expect.

Carbamates↗
PubMedDate not supplied

The underuse of insulin therapy in North America.

At least 8% of the combined population of the United States (US) and Canada have diabetes, and in about one-third of these people, the disease is undiagnosed [1]. Diabetes is not evenly distributed geographically, and there is surprisingly little consensus among categories of medical providers as to when and how intensive insulin therapy should be initiated. Although some physicians worry that insulin therapy may promote insulin resistance or increase the risk of cardiovascular events, the best current clinical evidence suggests that such fears are largely unfounded. Similarly, new evidence shows that the weight gain associated with insulin therapy is by no means always dramatic or progressive. The view that insulin is not effective in type 2 diabetes, although common in the US, is not shared by physicians experienced and skillful in its use and is refuted by recent clinical studies. Promising new patterns of insulin use in type 2 patients are emerging in the US: the availability of insulin as a single dose, rather than moving directly to multiple daily injections; the practice of continuing rather than stopping oral agents when an evening insulin dose is added; and the use of new insulins and insulin-sensitizing agents that facilitate therapy and increase its effectiveness. Several new treatment options are discussed.

Canada↗
PubMedDate not supplied

Exenatide elicits sustained glycaemic control and progressive reduction of body weight in patients with type 2 diabetes inadequately controlled by sulphonylureas with or without metformin.

BACKGROUND: In two placebo-controlled 30-week trials, treatment with exenatide reduced HbA(1c) and body weight in patients with type 2 diabetes in the context of sulphonylurea (SU) or SU plus metformin (MET) as background treatment. This analysis examines the effects of 82 weeks of exenatide treatment for participants in these earlier 30-week trials. METHODS: Data were pooled from the two pivotal trials of exenatide added to SU or SU plus MET. Both 30-week, placebo-controlled trials of 5 microg or 10 microg exenatide b.i.d. were followed by 52-week open-label, uncontrolled extension studies in which all participants received 10 microg exenatide b.i.d. and continued prior oral therapies. This interim analysis includes data for 222 patients who completed 82 weeks of exenatide treatment (61% M, age 57 +/- 10 y, weight 99 +/- 21 kg, BMI 34 +/- 6 kg/m(2), HbA(1c)8.4 +/- 1.0% [mean +/- SD]). RESULTS: Reduction in HbA(1c) from baseline to week 30 (-0.8 +/- 0.1% and -1.0 +/- 0.1% for 5 microg b.i.d. and 10 microg b.i.d., respectively [mean +/- SE]) was sustained up to week 82 (-1.0 +/- 0.1%). Of 207 patients with baseline HbA(1c) > 7%, 44% achieved HbA(1c) < or = 7% at week 82. Reduction of body weight from baseline to week 30 (-1.4 +/- 0.3 kg and -2.1 +/- 0.3 kg for 5 microg b.i.d. and 10 microg b.i.d., respectively) was progressive up to week 82 (-4.0 +/- 0.3 kg). The most frequent adverse events were nausea and hypoglycaemia, both generally mild to moderate in intensity. CONCLUSIONS: Exenatide added to maximally effective doses of SU or SU plus MET resulted in a sustained reduction in HbA(1c) and a progressive reduction in weight over 1 1/2 years.

Adolescent↗
PubMedDate not supplied

The Treat-to-Target Trial and related studies.

OBJECTIVE: To describe the rationale for, and the findings of, the Treat-to-Target Trial and to compare its results with those of two subsequent studies based on the same concepts. METHODS: The 24-hour pattern of hyperglycemia in type 2 diabetes is presented, and its separate components are identified in an attempt to help optimize therapeutic interventions for diabetes. In addition, the treat-to-target concept, including glycemic outcomes and potential adverse effects, is discussed. RESULTS: Using a hemoglobin A1c (A1c) value of 7% as a treatment goal based on evidence from interventional studies and a fasting plasma glucose level of 100 mg/dL as a target for titration of dosage of basal insulin, the Treat-to-Target Trial tested two hypotheses. It confirmed that addition of basal insulin to previously unsuccessful oral therapies can, using a simple algorithm, restore glycemic control to 7% A1c or better in most patients with type 2 diabetes. It also confirmed that a long-acting insulin analogue, glargine, causes less hypoglycemia than human NPH insulin when used in this way. Two subsequent studies using similar treatment algorithms showed comparable ability to improve glycemic control but also demonstrated more frequent unwanted effects of insulin treatment when a different comparator regimen was used to initiate therapy than when a glargine-based regimen was used. CONCLUSION: Initiation of insulin therapy with structured titration to glycemic targets can frequently, but not always, restore glycemic control in patients with type 2 diabetes when orally administered agents are no longer successful alone. Future trials should include hypoglycemia and weight gain as specific, objectively measured endpoints to assess their importance as adverse effects of titrating insulin dosage to target. Studies are needed to assess ways to control postprandial as well as basal hyperglycemia and thus enable almost all patients with type 2 diabetes to reach A1c targets.

Blood Glucose↗