Efficacy of combined treatments in NIDDM patients with secondary failure to sulphonylureas. Is it predictable?

Abstract

The treatment of NIDDM patients with secondary failure to sulphonylurea is a common problem. We performed a crossover study in 50 NIDDM patients with secondary failure to glibenclamide by comparing the addition to sulphonylurea of either a low-dose bedtime NPH insulin or a t.i.d. oral metformin and by analyzing treatment efficacy in relation to patient and disease characteristics. Both combined therapies clearly improved glycaemic control. HbA1 c were similarly reduced by the addition of either bedtime NPH insulin (7.6+/-0.34 vs 8.7+/-0.35, p<0.01) or metformin (7.6+/-0.22 vs 8.6+/-0.31, p<0.01). Also fasting plasma glucose (FPG) and post-prandial plasma glucose (PPPG) significantly decreased (p<0.01) with both treatments. Bed-time NPH insulin was more effective on FPG reduction than metformin (-36+/-2% vs -25+/-2%, p<0.01); in contrast, metformin addition was more effective on PPPG reduction than bedtime NPH insulin addition (-30+/-2% vs 20+/-3%, p<0.01). Serum cholesterol was marginally but significantly decreased after metformin (5.49+/-0.19 vs 5.91 +/-0.18 mM, p<0.05) but not after NPH insulin. Body weight increase was significantly greater after insulin addition than after metformin (1.47+/-0.25 Kg vs 0.64+/-0.17 p=0.02). All patients preferred the addition of metformin rather than NPH insulin. None of the measured clinical and metabolic variables (before treatment FPG and PPPG, HbA1 c, post-glucagon C-peptide levels, insulin sensitivity, patient age, BMI and diabetes duration) significantly correlated to the efficacy of the two combined treatments studied. In conclusion, in NIDDM patients with secondary failure to sulphonylureas the addition of either low-dose bedtime NPH insulin or t.i.d. metformin is similarly effective in improving glycaemic control. Metformin is better accepted by patients and provides a modest advantage in terms of body weight and cholesterol levels. The most common clinical and metabolic variables are not useful for predicting the efficacy of these two combined treatments.

Sarcoplasmic reticulum Ca2+ ATPase pump is a major regulator of glucose transport in the healthy and diabetic heart

“…These findings further suggest that the SERCA pump in the heart is a major regulator of not only cardiac but whole body glucose homeostasis, consistent with recent studies in liver tissue which also demonstrated that SERCA2b overexpression in the liver of obese mice lowered blood glucose concentration and improved glucose tolerance [41,42]. Taken together, these results suggest that activation of novel insulin-independent pathways regulating glucose transport could provide a much needed alternate therapeutic target for diabetic patients, for many of whom proper control of hyperglycemia by insulin-sensitizing therapy is lacking [43,44]. Since SERCA pump dysfunction contributes to the pathogenesis of diabetic cardiomyopathy, a common and insidious complication, overexpression of the SERCA pump is a promising gene therapy approach for the diabetic population [5,17,45].…”

The clinical utility of C‐peptide measurement in the care of patients with diabetes

“…There is evidence that more insulin-resistant patients with higher Cpeptide values have increased response to thiazolidinediones [105][106][107][108]. This does not appear to be the case for metformin, sulphonylureas and dipeptidyl peptidase-4 (DPP-4) inhibitors [84,105,[109][110][111].…”

A Practical Review of C-Peptide Testing in Diabetes

“…Higher MMTT stimulated c-peptide has been shown to be present in patients who respond to metformin and glibenclamide in combination but GST c-peptide did not predict response to glibenclamide alone [42, 43]. High fCP is associated with response to the thiazolidinediones, rosiglitazone and pioglitazone, which is in keeping with their action of reducing insulin resistance [44, 45].…”