Lecture 39
PRODUCT MOA
HYPOGLYCEMIC AGENTS
Fenugreek  Fibrous seeds may affect GI
transit time, slowing glucose
absorption (bulk laxative)
 4-hydroxy-isoleucine in the
seed stimulates glucose-
dependent insulin secretion
(hypoglycemic effects)
Gymnema  Enhances insulin release from
Sylvestre beta cells
 Decreases intestinal
(Gurmar) absorption of glucose
 Use leaves of the plant
Bitter melon  Believed to have similar
(Momordica effects to bovine insulin
charantia)
INSULIN SENSITIZERS:
Chromium  Cofactor for insulin function:
o Helps transport glucose
(also used in into cell by increasing
weight loss insulin binding
products) o Increases number of
insulin receptors
o May enhance insulin
sensitivity by activating
intracellular signalling
pathways
 Chromium deficiency has
similar features to diabetes
Cassia cinnamon  Promotes insulin release and
enhances insulin receptor
sensitivity (animal studies)
MISC.
Alpha lipoic acid  Coenzyme involved in carb
metabolism (naturally
synthesized in mitochondria)
 Antioxidant properties
(regenerate other
antioxidants like Vit E and C)
 Improves insulin sensitivity
(conflicting)
White mulberry  Leaf extract inhibits alpha-
glucoside in gut, preventing
(also used in absorption of carbs  lower
weight loss post-prandial BG
products)
Glucomannan or  Root of elephant yam
PGX  Highly viscous soluble fiber
that absorbs water  slows
(also used in absorption of carbs  slows
weight loss down release of sugars in gut
products)
NHPs in DM
DOSE AND DURATION EFFICACY
 2.5 – 15 g daily  In combo with sulfonylureas:
 Capsules come in ↓ FBG, HbA1C by 0.5%
600 mg – 1 g  Systemic review: ↓FBG
 Crushing seeds vital to (0.96 mmol/dL)
release viscous gel  Prediabetics: ↓ post-
fiber prandial & fasting BG, ↑
serum insulin, RRR of
developing T2DM 0.6
o Poor study, each was
own control
 200 mg bid used for  ↓ HbA1c, cholesterol, TGs,
up to 20 months dose of hypoglycemic drugs
o Poor study (no R, DB)
 Small studies, mixed results
 200 – 1400 ug used  HbA1C ↓ by 0.58%
for up to 6 months o Picolinate salt: -0.6%
 Use picolinate salt o Brewers yeast: -1.85%
(better absorption and  FBG ↓ by 1.13
bioavailability)  TG: ↓ by 0.3
 Food sources:  HDL: ↑ by 0.12
broccoli, grape juice,
whole wheat muffin,
red wine, Brewers’
yeast
 Up to 6 g/d of cassia  Insufficient evidence
cinnamon o ↓ FBG (-1.36), LDL
 NOTE: most stores sell (-0.52), TG (-1.42);
cinnamon bark (C. ↑ HDL-C (0.09) – all ss
verum) instead but clinical
significance??
o No improvement in
HbA1C
 600 mg (divided  Improved nerve conduction
doses) up to 2 years velocity & diabetic
 May take 3-5 weeks peripheral neuropathy sx
for symptom relief (pain, burning)
 Doesn’t lower HbA1C
 1g powdered leaf  Limited
before a meal o No change in HbA1C
o ↓ post-prandial BG
 ↓ in FBG
o Poor methods
Eccott
SAFETY
 Well tolerated
 Diarrhea, flatulence
 Contraindicated in pregnancy
(uterine stimulant)
 Avoid in thyroid conditions
(hypothyroid effects)
 Caution with anti-platelet/
coagulants (contains coumarin
derivative) = ↑ risk of
bleeding/bruising
 Monitor BG
 Avoid in pregnancy
 Caution pts taking
hypoglycemic drugs who eat
bitter melon
 Well tolerated (some GI upset)
 SAFE in pregnancy and
breastfeeding
 Contraindicated in renal
disease (excessive Cr may
damage kidneys)
 Space apart from
levothyroxine (binding
interaction)
 Very well tolerated
 Contains coumarin
constituents (high doses for
long time = liver damage)
 Avoid in pregnancy
 Higher doses more likely to
produce AEs (vertigo, NV)
 Avoid in pregnancy
 Avoid in pregnancy
 Well tolerated
 Monitor glucose & A1C
 May reduce drug absorption
(space drugs)
 Some cases of GI obstruction
o Take with LOTS of water
o Don’t use if difficulty
swallowing
 Avoid in pregnancy