Intervention: Metformin
Trial phase: Phase 1 | Phase 2
ATC code: A10BA02 | A10BD02 | A10BD03 | A10BD05 | A10BD07 | A10BD08 | A10BD10 | A10BD11 | A10BD13 | A10BD14 | A10BD15 | A10BD16 | A10BD17 | A10BD18 | A10BD20 | A10BD22 | A10BD23 | A10BD25 | A10BD26 | A10BD27
SMILES: CN(C)C(=N)NC(=N)N
Sex: Female
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 20
Group description: 10 stage 2 eligible mothers were randomly allocated to this arm. Mothers were instructed to thoroughly empty their breasts at least 8 times per day and to take the assigned study drug.

Standard care: Mothers will be instructed to thoroughly empty their breasts at least 8 times per 24 hours by breastfeeding, followed by breast expression with a combination of hand -expression and the use of a hospital-grade electric breast pump.

Metformin: The metformin arm will be consuming Glucophage XR (metformin hydrochloride extended release, 750 or 500 mg, encapsulated in #00 opaque capsules for 4 weeks according to the following schedule:

Days 1-7, one 750 mg capsule with evening meal (750 mg/day)
Days 8-14, three 500 mg capsule with evening meal (1500 mg/day)
Days 14-28 (or through completion of post-intervention data collection),four 500 mg capsules with evening meal (2000 mg/day)

The trial duration was28 days (with a +/- 3 day cushion)
Eligibility criteria:
Inclusion Criteria among mother-infant dyads:

Stage 1 Criteria (for participation in baseline measurement phase):

identified with low milk supply by a Cincinnati-area IBCLC
mother denies obvious cause of low milk supply such as pituitary disorder, breast surgery, severe lack of breast emptying (< 4 times per day), or failure to show any signs of lactogenesis
mother at least 20 years of age
infant is between 1 week and 2 calendar months old
mother gave birth to a single, healthy, term (>37 weeks gestation) infant
mother free of breast and nipple infections
mother lives within study catchment area
mother has not been diagnosed with Type 1 or Type 2 Diabetes Mellitus
mother willing to sustain consistent use of herbal galactogogues (such as fenugreek) during follow up measurements (2-4 weeks) as was consumed during the baseline measurements
mother not currently taking a prescription medication that may affect the hormones of lactation and not planning to initiate any such drug for at least the next 2-4 weeks.
mother has established pediatric care for the infant

Stage 2 maternal inclusion criteria (among those who meet Stage 1 criteria, to continue with enrollment into randomized controlled trial, goal, N=30 with replacement for non-completers to at least two weeks):

successful completion of baseline measurements (involving 24-hour test weighing of milk output and undergoing baseline measurements at the clinical research center, including providing fasting blood samples)
body mass index is >19.0 kg/m2 (i.e., not underweight)
evidence of likely insulin resistance, based on at least one of the following: mean fasting plasma glucose between 95.0 - 125.0 g/dL, inclusive; abdominal obesity; history of polycystic ovary syndrome; or history of gestational diabetes
estimated glomerular filtration rate > 60 mL/min
liver function in normal range (AST <= 37 U/L, ALT < 87 U/L, and total bilirubin <= 1.1 mg/dL
willingness to continue trying to lactate for the next 2-4 weeks
health history does not reveal illness/treatments for which metformin is contraindicated
participant is not currently being treated with metformin

Eligibility criteria for enrollment into abundant milk supply comparison group (goal, N=30, will be compared in baseline measurements).

Inclusion criteria:

exclusively feeding mother's own milk to infant, and presenting to Cincinnati area IBCLC with breastfeeding question or problem unrelated to milk supply
mother at least 20 years of age
infant is between 1 week and 2 calendar months old
mother gave birth to a single, term infant
mother free of breast and nipple infections
mother lives within study catchment area
mother has not been diagnosed with Type 1 or Type 2 Diabetes Mellitus
mother willing to sustain consistent use of herbal galactogogues (such as fenugreek) during baseline measurements
mother willing to avoid prescription medication that may affect the hormones of lactation