The effect of metformin treatment on gastric acid secretion and gastrointestinal hormone levels in normal subjects

Molloy, Anne M.; Ardill, Jes; Tomkin, G. H.

doi:10.1007/bf00421851

Cited by 28 publications

(21 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The short time scale of development of intrinsic factor deficiency seemed more in keeping with a drug effect than a spontaneous event and the studies in normal volunteers were initiated to study the effect of metformin on gastric secretion. While there was no significant change in acid output, disagreeing with a previous report of augmentation [6] of intrinsic factor output, there were striking individual responses with dramatic falls in intrinsic factor output in four subjects.…”

Section: Discussioncontrasting

confidence: 99%

Malabsorption of vitamin B12 and intrinsic factor secretion during biguanide therapy

et al. 1983

View full text Add to dashboard Cite

Summary. In a survey of 46 randomly selected diabetic patients on biguanide therapy, 30% had malabsorption of vitamin B12. Withdrawal of the drug resulted in normal absorption in only half of those with malabsorption. In most patients with persistent malabsorption, the results of absorption tests with exogenous intrinsic factor suggested the diagnosis of coincidental intrinsic factor deficiency. Further considerations, however, led to the concept that biguanides can induce malabsorption by two different mechanisms. One of these is temporary and unrelated to intrinsic factor secretion and the other is permanent and mediated by depression of intrinsic factor secretion. Key-words:Biguanides, phenformin, metformin, vitamin B12 , intrinsic factor deficiency, malabsorption.Malabsorption of vitamin B12 is a well-known complication of biguanide therapy. Any disease causing malabsorption may, however, occur in diabetic patients and an interesting feature of studies of vitamin B12 absorption in diabetic patients on biguanides is the apparent rarity of such conditions. As we had formed an impression that anaemias not related to biguanide therapy occurred more often than might be expected, we decided to test this by a study of the absorption of vitamin Ba2 by diabetic patients on biguanides and extended this to the effects of metformin on the gastric secretory capacity of normal subjects. Subjects and Methods SubjectsForty-six diabetic patients on biguanide therapy were selected randomly for a survey of the capacity to absorb vitamin B12. Thirty-eight were female (aged 40-72 years, average 58 years) and eight were male (aged 45-72 years, average 59 years). The ratio of males to females is representative of the sex distribution of obese non-insulin-dependent diabetic patients attending the clinic. The average age of onset of diabetes was 50years in males (range 38-67years) and 51 years in females (range 32-75 years).Twenty-eight patients (24 males, four females) were studied on metformin 13 (three males, ten females) on phenformin and five (one male, four females) while on both drugs at different times. The dose of metformin ranged from i to 3 g daily, and the duration of treatment at the time of study was from 1 to 6 years; the dose of phenformin was 50 mg twice daily and the duration of treatment ranged between 3 months and 6 years. MethodsThe capacity to absorb vitamin B~2 was measured with a scanning type whole body monitor utilising six sodium iodide detectors each 15.2 cm diameter and 10.2 cm thick housed in a custom built room with 15 cm thick steel walls. The statistical accuracy of a result is + 5% (i.e.: 5 + 5%, 20 _+ 5%, etc.) and the mean coefficient of variation between results is 26%. A control series absorbed between 26% and 89% (mean + SD: 50.6 -!-_ 14.7%) of 1 Ixg radioactive cyanocobalamin and for routine purposes absorption of < 30% is regarded as subnormal. After preliminary scanning, oral doses of 1 gg, 0.25 j_tCi, 57Co or 58Co cyanocobalamin were given after a t2-h fast which was continued for a further...

show abstract

Section: Discussioncontrasting

confidence: 99%

Malabsorption of vitamin B12 and intrinsic factor secretion during biguanide therapy

et al. 1983

View full text Add to dashboard Cite

show abstract

“…While the effects of metformin on increasing GLP-1 secretion have been known for some time (24)(25)(26)(27), its significance is debated. Interestingly, the increase in plasma GLP-1 levels resulting from metformin administration is similar to that of a DPP-4i (20) and thus could explain much of the glucoselowering effect of metformin.…”

Section: Discussionmentioning

confidence: 99%

The Primary Glucose-Lowering Effect of Metformin Resides in the Gut, Not the Circulation: Results From Short-term Pharmacokinetic and 12-Week Dose-Ranging Studies

et al. 2015

View full text Add to dashboard Cite

OBJECTIVEDelayed-release metformin (Met DR) is formulated to deliver the drug to the lower bowel to leverage the gut-based mechanisms of metformin action with lower plasma exposure. Met DR was assessed in two studies. Study 1 compared the bioavailability of single daily doses of Met DR to currently available immediaterelease metformin (Met IR) and extended-release metformin (Met XR) in otherwise healthy volunteers. Study 2 assessed glycemic control in subjects with type 2 diabetes (T2DM) over 12 weeks. RESEARCH DESIGN AND METHODSStudy 1 was a phase 1, randomized, four-period crossover study in 20 subjects. Study 2 was a 12-week, phase 2, multicenter, placebo-controlled, dose-ranging study in 240 subjects with T2DM randomized to receive Met DR 600, 800, or 1,000 mg administered once daily; blinded placebo; or unblinded Met XR 1,000 or 2,000 mg (reference). RESULTSThe bioavailability of 1,000 mg Met DR b.i.d. was ∼50% that of Met IR and Met XR (study 1). In study 2, 600, 800, and 1,000 mg Met DR q.d. produced statistically significant, clinically relevant, and sustained reductions in fasting plasma glucose (FPG) levels over 12 weeks compared with placebo, with an ∼40% increase in potency compared with Met XR. The placebo-subtracted changes from baseline in HbA 1c level at 12 weeks were consistent with changes in FPG levels. All treatments were generally well tolerated, and adverse events were consistent with Glucophage/Glucophage XR prescribing information. CONCLUSIONSDissociation of the glycemic effect from plasma exposure with gut-restricted Met DR provides strong evidence for a predominantly lower bowel-mediated mechanism of metformin action.

show abstract

“…Enhanced plasma levels of the insulinotropic hormone glucagon-like peptide 1 (GLP-1) have been reported after metformin treatment in humans and in preclinical models. [55][56][57] Among other beneficial antidiabetic effects, GLP-1 suppresses the hyperglycemic action of glucagon, causing decreased HGO and lower circulating glucose levels. Recent studies by Smith and colleagues 41,58 demonstrated that olanzapine-, clozapine-and quetiapine-induced glucose dysregulation was associated with decreased GLP-1 production and enhanced glucagon secretion, leading to stimulated HGO.…”

Section: Discussionmentioning

confidence: 99%

Differential effects of 3 classes of antidiabetic drugs on olanzapine-induced glucose dysregulation and insulin resistance in female rats

Boyda

Procyshyn²,

Tse

et al. 2012

J Psychiatry Neurosci

View full text Add to dashboard Cite

The effect of metformin treatment on gastric acid secretion and gastrointestinal hormone levels in normal subjects

Cited by 28 publications

References 8 publications

Malabsorption of vitamin B12 and intrinsic factor secretion during biguanide therapy

Malabsorption of vitamin B12 and intrinsic factor secretion during biguanide therapy

The Primary Glucose-Lowering Effect of Metformin Resides in the Gut, Not the Circulation: Results From Short-term Pharmacokinetic and 12-Week Dose-Ranging Studies

Differential effects of 3 classes of antidiabetic drugs on olanzapine-induced glucose dysregulation and insulin resistance in female rats

Contact Info

Product

Resources

About