Term
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Definition
baseline characteristics: 62yo, 39% male, history of CVD: 35%, BMI: 32, A1c: 8.1%, on insulin: 35%, duration of DM: 10 years
follow: 2.5 years, terminated early (started to see an increase in mortality for those patients who were treated more aggressively)
primary outcomes: nonfatal MI and stroke, CVD death
A1c target: <6% vs 7-7.9%
findings: increase in mortality in intensive arm compared to standard. Similar increase in CV deaths. Primary outcomes was reduced in intensive control because of the reduction in nonfatal MI, however not statistically significant when study terminated. Separation in A1c was very limited in time ~3-6 months |
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Term
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Definition
baseline characteristics: 66yo, 42% male, history of CVD: 32%, BMI: 28, A1c: 7.2%, on insulin: 1.5%, duration of DM: 2 years
follow: 5 years
primary outcomes: microvascular and macrovascular (nonfatal MI and stroke, CVD death) - composite of both
A1c target: <6.5% vs local standards
findings: intensive glycemic control significantly reduced the primary endpoint, although due to reduction in MICRO, not statistically significant reduction in MACRO. No increase in overall or cardiovascular disease mortality in the intensive compared to standard |
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Term
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Definition
baseline characteristics: 60yo, 97% male, history of CVD: 42%, BMI: 31, A1c: 9.4%, on insulin 52%
follow: 5.6 years
primary outcomes: nonfatal MI and stroke, CVD death, hospitalization for heart failure, revascularization
A1c target: <6% (action if >6.5%) vs planned separation of 1.5%
findings: cumulative incidence of primary outcome was not statistically significant in the intensive arm. More CVD deaths int he intensive arm than in the standard arm, but not statistically significant. Patients with diabetes ~<12 years had CVD benefit in the intensive glycemic control. Those with DM longer had neutral or negative effects. |
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Term
initial therapy
lifestyle to decrease weight and increase activity; 1-2% expected decrease in A1c; broad benefits; disadvantages - insufficient for most within first year
metformin: 1-2% expected decrease in A1c; advantages - weight neutral; disadvantages - GI side effects, contraindicated with renal insufficiency |
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Definition
| Tier 1, Step 1 management of T2DM |
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Term
additional therapy
insulin (in addition to lifestyle and metformin): 1.5-3.5% expected decrease in A1c; advantages - no dose limit, rapidly effective, improved lipid profile; disadvantages - 1-4 injections daily, monitoring, weight gain, hypoglycemia, analogues are expensive
OR
sulfonylureas (in addition to lifestyle and metformin): 1-2% expected decrease in A1c; advantage - rapidly effective; disadvantages - weight gain, hypoglycemia |
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Definition
| Tier 1, Step 2 management of T2DM |
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Term
lifestyle + metformin +...
TZDs: 0.5-1.4% expected decrease in A1c; advantages - improved lipid profile (pioglitazone), potential decrease in MI (pioglitazone); disadvantages - fluid retention, CHF, weight gain, bone fractures, expensive, potential increase in MI (rosiglitazone)
GLP-1 agonist: 0.5-1% expected decrease in A1c; advantage - weight loss; disadvantage - 2 injections daily, frequent GI side effects, long-term safety not established, expensive |
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Definition
| Tier 2 management of T2DM |
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Term
enhances insulin sensitivity of both hepatic and peripheral tissues (muscle)
increase uptake of glucose into the insulin sensitive tissues
no DIRECT effect on beta cells
referred to as an insulin sensitizer
does not effect the secretion of insulin, so does not cause hypoglycemia
fasting plasma glucose lowering: 60-80 mg/dl
A1c lowering: 1.5-2%
glucose target: fasting >>>>>> possible post prandial (limited data to support) |
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Definition
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Term
start low and go slow - consensus indicates to start at 250mg BID (do this to decrease GI problems) and titrate upwards (1-2 weeks titration is beneficial to not waste time)
XR formulations may help with GI side effects
max CLINICALLY effective dose is 2000mg/d
max PACKAGE INSERT dose is 2550mg/d |
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Definition
| dosing pearls of metformin |
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Term
GI effects: abdominal discomfort, stomach upset and/or diarrhea in ~30% of patients. Transient in most cases improving over weeks of use. Anecdotally, XR formulation may have less GI issues
taste aversion: metallic taste may occur and may persist throughout treatment. This is not harmful and not bothersome would recommend for patient to continue
hypoglycemia: rare but possible, especially with intense exercise or in combination with other oral DM medications (SFU or insulin)
LACTIC ACIDOSIS: rare; clinical presentation - flu-like symptoms, N/V, bloating, hyperventilation, anemia
DO NOT USE THIS DRUG IN:
Unstable/decompensated CHF PATIENTS, hypoxic states, shock: due to decrease tissue perfusion
severe liver disease or extreme alcohol usage: reduced removal of lactic acid in liver
radio-contrast dye patients: must discontinue product a few days before and/or after depending upon procedure. these dyes are renal toxic so don't want to take metformin during a time of decreased kidney function (increased risk of lactic acidosis)
renal insufficiency: ****do not use if female and SCr >1.4 mg/dl or if male and SCr >1.5mg/dl***** (not able to excrete lactic acid)
monitoring: baseline and annual/periodic Chem7, LFT, and CBC |
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Definition
| adverse effects/monitoring or metformin |
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Term
female SCr > 1.4mg/dl
male SCr >1.5mg/dl |
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Definition
| for what SCr levels can metformin not be used? |
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Term
stimulates insulin release from pancreatic beta cells (binds to the SUR receptor on pancreatic beta cells).
enhances secretion of insulin from the pancreas -> travels via the portal vein and subsequently suppresses hepatic glucose production
fasting plasma glucose lowering: 60-70 mg/dl
A1c lowering: 1.5-2%
glucose target: fasting |
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Definition
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Term
never use 1st generation
if new start: would recommend glipizide or glimepiride above glyburide
glyburide has longer half life and more active metabolites = increase chance of hypoglycemia
glipizide and glimepiride have shorter half lives and less active metabolites, not as much renal clearance
may titrate every 2 weeks
max CLINICAL DOSE if 1/2 of max package insert dose
caution in elderly and renally impaired patients due to decreased clearance and increased risk of hypoglycemia |
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Definition
| dosing pearls of sulfonylureas |
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Term
hypoglycemia: pretreatment FPG is strong predictor of potential; at risk - renal/hepatic impairment, those who skip meals, exercise vigorously, lose substantial weight
hyponatremia: more so with 1st generation (TOLBUTAMIDE OR CHLORPROPAMIDE); at risk - >60 yo, female, concomitant use of diuretics
weight gain: at risk - anyone
monitoring: baseline Chem7 and then periodically |
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Definition
| adverse effects and monitoring of sulfonylureas |
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Term
per consensus: Tier 1, Step 2
may be 1st line if metformin is contraindicated
if + C peptide levels, then know beta cells are working (sulfonylureas stop working when patient loses beta cell function as the disease progresses. if the patient has had DM for 15 years, won't work as well as newly diagnosed)
great start is patient not worried about weight gain and glucose is extremely elevated as it can lower SMBGS faster than metformin, however metformin has stronger data for its use if no contraindications |
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Definition
| clinical place of sulfonylureas |
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Term
per consensus: Tier 1, Step 2
may be 1st line if metformin is contraindicated
if + C peptide levels, then know beta cells are working (sulfonylureas stop working when patient loses beta cell function as the disease progresses. if the patient has had DM for 15 years, won't work as well as newly diagnosed)
great start is patient not worried about weight gain and glucose is extremely elevated as it can lower SMBGS faster than metformin, however metformin has stronger data for its use if no contraindications |
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Definition
| clinical place of sulfonylureas |
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Term
binds to PPARy primarily located in fat or vascular cells
enhance insulin sensitivity at muscle, liver and fat tissues indirectly
cause preadipocytes to differentiate into mature fat cells in SQ fat stores (taking out of visceral and moving to SQ)
small fat cells are more sensitive to insulin and more able to store free fatty acids
a flux of free fatty acids out of the plasma, visceral fat, and liver into SQ fat, and less insulin-resistant storage tissue
fasting plasma glucose lowering: 60-70 mg/dl
A1c lowering: 1.5% at 6 months
glucose target: fasting |
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Definition
| MOA of thiazolidinediones (TZD) - pioglitazone and rosiglitazone |
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Term
never use ROSIGLITAZONE: can only use IF all other diabetes medications have failed or not an option AND the provider has documented the education of risks associated with medication
ONLY would recommend PIOGLITAZONE: can still cause heart failure however no documented cardiovascular detriments
may titrate q4 weeks, however may take 16-18 weeks to see max dose effect
side effects are dose dependent, therefore start on lowest dose possible to achieve the outcome of better glucose support
pioglitazone has better effects to lower TGs, increase HDL, and other metabolic parameters |
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Definition
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Term
liver abnormalities: no evidence of hepatotoxicity with newer agents (pioglitazone and rosiglitazone) in an analysis of 5000 patients, however case reports have been documented. an increase in ALT did occur however improved once drug was discontinued
At baseline if ALT > 2.5x uln -> DO NOT START AGENT
During therapy if ALT > 3x uln -> discontinue drug
edema: retention of fluid - peripheral vasodilation and/or improved insulin sensitization with a resultant increase in renal Na/H2O retention; more common when used in combination with insulin; dose related, therefore may reduce dose and/or add diuretic if needed; DO NOT USE IN HF III AND IV; caution use of rosiglitazone in HF I and II due to increased risk of cardiovascular events
weight gain: dose related; highest weight increase in patients on insulin as combination therapy
ovulation
macular edema
fractures in FEMALES
monitoring: baseline LFT (AST and ALT) then q3-6 months and then periodically |
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Definition
| adverse effects and monitoring of TZDs |
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Term
per consensus Tier 2, Step 2
pioglitazone may be considered if other recommended agents such as metformin, SFUs, insulin, or GLP agonists are not an option
often times added on as 3rd line, especially if patient has issues with lipid parameters and no history of heart disease and patient wants to stay off insulin |
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Definition
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Term
per consensus Tier 2, Step 2
pioglitazone may be considered if other recommended agents such as metformin, SFUs, insulin, or GLP agonists are not an option
often times added on as 3rd line, especially if patient has issues with lipid parameters and no history of heart disease and patient wants to stay off insulin |
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Definition
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Term
competitively inhibit enzymes in the small intestines
this action delays the breakdown of sucrose and complex carbohydrates
fasting plasma glucose lowering: no effect
A1c lowering: 0.3-1%
glucose target: postprandial 40-50 mg/dl |
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Definition
| MOA of alpha-glucosidase inhibitors |
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Term
start low on dosage: 25mg QD, BID, TID then titrate up weekly (depends on meals)
if patient does not eat/skips a meal -> does not take medication
to be given at first bite of meal
instruct patient to have low carb meals to reduce side effects of GI issues
may use in combination with sulfonylureas but not in combination with SHORT ACTING SECRETAGOGUES - NATEGLINIDE AND REPAGLINIDE
in order to treat hypoglycemic episodes, must give simple sugar due to MOA of this class |
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Definition
| dosing pearls of alpha-glucosidase inhibitors |
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Term
GI effects: Flatulence (distal intestinal degredation of undigested carbs by microflora which results in gas), bloating, abdominal discomfort, diarrhea (LIMITS USE)
CONTRAINDICATED in patients with inflammatory bowel disease or short-bowel syndrome or other bowel obstruction histories
hypoglycemia: must give simple glucose due to MOA of drug
liver abnormalities: possibility of elevated LFT at higher doses; dose and weight related
monitoring: baseline LFTs, q3 months for the first year and periodically; baseline Chem7 and periodically |
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Definition
| adverse effects and monitoring of alpha-glucosidase inhibitors |
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Term
not noted in consensus statement, however EXCELLENT agent if patient can tolerate and having POSTPRANDIAL ISSUES
can only reduce A1c by up to 1%, therefore if above 8% would not readily recommend this agent
great for patients with high carbohydrate loads for meals |
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Definition
| clinical place for alpha-glucoseidase inhibitors |
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Term
the best agent for new diagnosis unless contraindicated
only agent recommended for those who have pre-diabetes
inexpensive, greatest oral agent A1c reduction, safe, and mostly tolerated |
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Definition
| clinical place for metformin |
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Term
work similarly to sulfonylureas, however both these agents NEED GLUCOSE to stimulate insulin secretion
as glucose levels diminish to normal, stimulated insulin secretion diminishes
fasting plasma glucose lowering: not effected
A1c lowering: nateglinide - 0.4-1%, repaglinide - 1.5-2%
glucose target: post prandial |
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Definition
| MOA of short acting secretagogues (nateglinide and repglinide) |
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Term
take 30 minutes before a meal 1-4x/day
if patient does not eat or skips a meal -> does not take medication
both agents can be used in renal insufficiency
caution in hepatic impairment
DO NOT USE in combination with sulfonylureas (similar MOA)
may titrate q2 weeks |
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Definition
| dosing pearls of short acting insulin secretagogues (nateglinide and repaglinide) |
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Term
hypoglycemia: main side effect however less vs sulfonylureas (due to half life and glucose sensitive release of insulin); at risk - renal/hepatic impairment, those who skip meals, exercise vigorously, lose substantial weight
weight changes: 1-3 kg increase; clinically not noticeable
monitoring: baseline Chem7 then periodically |
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Definition
| adverse effects and monitoring of short acting insulin secretagogues (nateglinide and repaglinide) |
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Term
CYP450 inducers/inhibitors
gemfibrozil: doubles t1/2 of repaglinide and may result in prolonged hypoglycemic reactions; would not warrent change in therapy, however more monitoring |
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Definition
| interactions of short acting insulin secretagogues (nateglinide and repaglinide) |
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Term
not noted in consensus statement, however EXCELLENT agent if patient is having POSTPRANDIAL ISSUES
adherence may be a concern due to dosing
Repaglinide give greater A1c reduction than Nateglinide, if >8.5% would not readily recommend this agent
would go to this postprandial agent before alpha-glucosidase inhibitors, just b/c of side effect profile |
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Definition
| clinical place of short acting insulin secretagogues (nateglinide and repaglinide) |
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Term
incretin enhancers
endogenous GLP-1 is rapidly degraded by DPP IV within 1-5 minutes
therefore, blocking the catabolic mechanism of GLP-1 would allow decreased plasma clearance and increase T1/2 of endogenous GLP-1
possible increase in beta cell mass
increases satiety
slows gastric motility
slows glucagon production
increases insulin secretion
A1c lowering 0.5-1%
glucose target: fasting = postprandial
primary site of action = pancreas/gut |
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Definition
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Term
renal dosing is needed for both sitagliptin and saxagliptin
sitagliptin renal dosing is more involved than saxagliptin
titrate q1-2 weeks
greater A1c% reduction in patients with higher baseline A1c
very costly agent - do not go to first!! |
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Definition
| dosing pearls of DPP4 inhibitors |
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Term
hypoglycemia: rare - more common when in combination with sulfonylureas. many times the sulfonylurea dose should be reduced, but the exact amount is not stated
weight: neutral effects or some weight reduction
monitoring: baseline Chem7 then periodically |
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Definition
| adverse effects and monitoring of DPP4 inhibitors |
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Term
digoxin: sitagliptin may increase AUC of digoxin however not sure of clinical recommendations
saxagliptin does not affect it |
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Definition
| drug interactions of DPP4 inhibitors |
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Term
not noted in the consensus statement, however can help with FASTING = POSTPRANDIAL, so may use as ADD-ON or monotherapy if no other option can be used
if SFU cannot be used may be great place but very costly
less than or equal to 1% A1c reduction
COSTLY $5/pill |
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Definition
| clinical place of DPP4 inhibitors |
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Term
persons with DM have decreased levels of GLP-1; however sensitivity to GLP-1 is able to occur
GLP-1 is a potent insulin secretagogue and lowers blood glucose in the fasting and post prandial states
GLP-1 effects are glucose dependent
1) increasing insulin release and suppressing glucagon response in the presence of glucose. Helps to restore 1st phase insulin release
like amylin, GLP-1 agonsits 2) can slow gastric emptying
3) suppress food intake and decrease glucagon secretion
actually has actions to restore beta cell function and increase beta cell mass (more testing is needed)
A1c lowering: Exenatide - 0.4-0.9%; Liraglutide - 0.8-1.2%
glucose target: postprandial >>>> fasting (exenatide); fasting = postprandial (liraglutide) |
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Definition
| MOA of incretin mimetics (GLP-1 agonist) |
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Term
titrate q4 weeks to achieve glycemic goals
T2DM and trying to decide about possibly starting incretins of amylin -> if patient is on insulin go with amylin products. if just on oral, go with incretins
consider reducing dose of insulin secretagogues when starting agents
no data on concurrent use of insulin or other oral therapies
DO NOT administer after a meal |
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Definition
| dosing pearls of GLP-1 agonists |
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Term
hypoglycemia: dose dependent and related to other oral therapies. more hypoglycemia with sulfonylureas than metformin
cancers: medulary thyroid carcinoma and multiple neoplasia syndrom type 2 (liraglutide only - animal studies)
GI effects: N/V - subsides over time (BOTH AGENTS); kidney insufficiency - do not use in CrCl < 30mg/dl
weight loss: dose dependent from 0.3kg-2.5kg at 30 weeks
monitoring: baseline and periodic Chem7 |
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Definition
| adverse effects and monitoring of GLP-1 agonists |
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Term
more beneficial for weight loss, more costly, no hypoglycemia as a side effect
consensus indicates Tier 2 Step 2
you can use this therapy prior to starting insulin in patients
liraglutide has better A1c reduction and only dosed QD
if A1c >9% may not be the best agent over insulin, however may be a great agent if refuses insulin
weight loss is a good side effect of this |
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Definition
| clinical place of GLP-1 agonists |
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Term
amylin is produced and stored by beta cells in the pancreas
not only dose insulin (beta cells) and glucagon (alpha cells) help with the interplay of glucoregulatory hormones, amylin has a different MOA
1) restrains the rate of gastric emptying, thereby slowing the rate of intestinal CHO absorption to match the rate of glucose uptake by the peripheral tissues
2) amylin also suppresses hepatic glucose output by inhibiting glucagon secretion after meal ingestion
3) increases insulin secretion
4) transmits signal to the CNS to induce postprandial satiety in direct portion to food intake
A1c lowering: 0.4-0.6%
glucose target: postprandial |
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Definition
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Term
have to reduce each postprandial insulin by 50% when taking amylin to avoid hypoglycemia
take with meals - package insert recognizes a meal as 250 calories or 30 g of CHO
lots of SMBG testing first week
need glucagon Rx on hand
DO NOT MIX WITH INSULINS
DO NOT GIVE TO PATIENTS WITH GI ISSUES (gastroparesis or motility drugs) |
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Definition
| dosing pearls of pramlintide |
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Term
start 0.1-0.2 units/kg/day
continue orals or start to reduce orals |
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Definition
| dose of insulin to start D2DM patients who are following the bedtime insulin daytime orals (BIDO) plan |
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Term
0.5-1 unit/kg/day
split this dose 50/50 for basal and bolus |
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Definition
| dose of insulin to start a T2DM patient who is taking insulin as a monotherapy |
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