title: Add-on therapies to metformin in type 2 diabetes: what modulates the respective decrements in postprandial and basal glucose?
abstract: BACKGROUND
  Oral hypoglycemic agents (OHAs) are usually divided into postprandial and basal drugs. As their actions are probably more complex, it is important to ascertain which factors can modulate their effects.
  
  
  METHODS
  Thirty-one type 2 diabetes patients treated with metformin (glycosylated hemoglobin [HbA1c] 6.5-9%; median, 7.3%) and enrolled in two randomized controlled studies were allocated to either rosiglitazone (Group 1, n = 8) or glimepiride (Group 2, n = 7) and to either vildagliptin or sitagliptin (Group 3 considered as a whole, n = 16). All patients were investigated using continuous glucose monitoring at baseline and after 8-12 weeks of add-on therapy. Areas under the 24-h glycemic profile curves (AUCs) were determined for assessing postprandial (AUCpp), basal (AUCb), and total (AUCtotal) hyperglycemia. After calculation of decrements in AUCs (∂AUCs) from baseline to end of treatment periods, the following contribution ratios of postprandial and basal decrements to the overall glucose decrement were determined: ∂AUCpp/∂AUCtotal and ∂AUCb/∂AUCtotal (%).
  
  
  RESULTS
  ∂AUCpp/∂AUCtotal and ∂AUCb/∂AUCtotal were negatively and positively, respectively, associated (R(2) = 0.195, P = 0.013) with baseline HbA1c. ∂AUCpp/∂AUCtotal was significantly higher (50.8 ± 4.8%) in patients with HbA1c <7.3% than in those with HbA1c ≥ 7.3% (27.0 ± 4.4%) (P = 0.001). After adjustment on baseline HbA1c, ∂AUCpp/∂AUCtotal was greater in Group 3 (44.0 ± 1.6%) than in Group 1 (32.1 ± 4%) and 2 (37.0 ± 3.1%) (P = 0.007).
  
  
  CONCLUSIONS
  Gliptins, glitazones and sulfonylureas concomitantly act on basal and postprandial glucose even though gliptins are more efficient on postprandial glucose. HbA1c appears as a reliable factor for predicting the respective decrements of these two parameters and thus for guiding the choice between the aforementioned drugs.
authors: Laboratory of Human Nutrition and Atherosclerosis, Institute of Clinical Research, University of Montpellier 1, Montpellier, France. louis.monnier@inserm.fr
authors: Louis
authors: L
authors: Monnier
authors: Claude
authors: C
authors: Colette
authors: Andrea
authors: A
authors: Comenducci
authors: Denis
authors: D
authors: Vallée
authors: Sylvie
authors: S
authors: Dejager
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D019540:Area Under Curve; D001481:Basal Metabolism; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000494:pharmacology*; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage / Q000494:pharmacology; D019518:Postprandial Period / Q000187:drug effects; D011719:Pyrazines / Q000008:administration & dosage / Q000494:pharmacology; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology; D000077154:Rosiglitazone; D000068900:Sitagliptin Phosphate; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000494:pharmacology; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000494:pharmacology; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology; D000077597:Vildagliptin
chemical_list: D000218:Adamantane; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D009570:Nitriles; D011719:Pyrazines; D011759:Pyrrolidines; D000077154:Rosiglitazone; D000068900:Sitagliptin Phosphate; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; D014230:Triazoles; D000077597:Vildagliptin; C517652:hemoglobin A1c protein, human; C057619:glimepiride