title: Current use of metformin in addition to insulin in pediatric patients with type 1 diabetes mellitus: an analysis based on a large diabetes registry in Germany and Austria.
abstract: BACKGROUND
  With increasing obesity in childhood and adolescence, weight gain, and insulin resistance become also more frequent in patients with type 1 diabetes mellitus (T1DM). Especially during puberty, insulin therapy often has to be intensified and higher insulin doses are necessary. Some studies point to a beneficial effect of metformin in addition to insulin in these patients. In order to describe current practice and possible benefits, we compared pediatric T1DM patients with insulin plus metformin (n = 525) to patients with insulin therapy only (n = 57 487) in a prospective multicenter analysis.
  
  
  METHODS
  Auxological and treatment data from 58 012 patients aged <21 yr with T1DM in the German/Austrian Diabetes Patienten Verlaufsdokumentation (DPV) registry were analyzed by multivariable mixed regression modeling.
  
  
  RESULTS
  Patients with additional metformin were older [median (interquartile range)]: [16.1 (14.1-17.6) vs. 15.2 (11.5-17.5) yr] with female preponderance (61.0 vs. 47.2%, p < 0.01). They had higher body mass index-standard deviation score (BMI-SDS) [+2.03 (+1.29 to +2.56) vs. +0.51 (-0.12 to +1.15); p < 0.01] and glycated hemoglobin (HbA1c) (9.0 vs. 8.6%, p < 0.01). Hypertension (43.7 vs. 24.8%) and dyslipidemia (58.4 vs. 40.6%) were significantly more prevalent. Adjusted insulin dose was significantly higher (0.98 vs. 0.93 IU/kg bodyweight). In a subgroup of 285 patients followed-up longitudinally (average treatment period 1.42 yr), addition of metformin resulted in a slight reduction of BMI-SDS [-0.01 (-2.01 to +1.40)], but did not improve HbA1c or insulin requirement.
  
  
  CONCLUSIONS
  Additional metformin therapy in T1DM is primarily used in obese females. Additional therapy with metformin was associated with minor benefits.
authors.affiliation: Department of Pediatrics II, University Children's Hospital Essen, Essen, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Konrad
authors.affiliation: Department of Pediatrics, ''Auf der Bult" Hannover, Hannover, Germany.
authors.forename: Nicolin
authors.initials: N
authors.lastname: Datz
authors.affiliation: Department of Pediatrics, Childrens Hospital Munchen Schwabing, München, Germany.
authors.forename: Ilse
authors.initials: I
authors.lastname: Engelsberger
authors.affiliation: Department of Pediatrics, University of Heidelberg, Heidelberg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Grulich-Henn
authors.affiliation: Department of Pediatric and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hoertenhuber
authors.affiliation: Department of Pediatrics, CJD Berchtesgaden, Berchtesgaden, Germany.
authors.forename: Burkhild
authors.initials: B
authors.lastname: Knauth
authors.affiliation: Department of Pediatrics, University of Düsseldorf, Düsseldorf, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Meissner
authors.affiliation: Department of Pediatrics, University Charite Berlin, Berlin, Germany.
authors.forename: Susanna
authors.initials: S
authors.lastname: Wiegand
authors.affiliation: Department of Pediatrics, University of Bonn, Bonn, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Woelfle
authors.affiliation: Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany.
authors.forename: Reinhard W
authors.initials: RW
authors.lastname: Holl
mesh_terms: D000293:Adolescent; D001317:Austria / Q000453:epidemiology; D015992:Body Mass Index; D002648:Child; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000150:complications / Q000453:epidemiology; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000150:complications / Q000453:epidemiology; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D007333:Insulin Resistance; D008137:Longitudinal Studies; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D050177:Overweight / Q000150:complications* / Q000453:epidemiology; D010818:Practice Patterns, Physicians'; D015995:Prevalence; D011446:Prospective Studies; D012042:Registries
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin
keywords: BMI; PCOS; diabetes registry; glycated hemoglobin; insulin resistance; metformin