E3: Diabetes Treatment
If someone is on metformin and you give them contrast, how long do you need to hold the next dose for?
****MUST HOLD DOSE FOR 48 HOURS after contrast****
What is the suffix of DPP-4 inhibitors? Examples?
-agliptins Sitagliptin (Januvia), linagliptin (Tradjenta), saxagliptin (Onglyza), alogliptin (Nesina)
He presents 3 months later. He is currently taking Lisinopril 10 mg and HCT 25 mg daily. Vitals today: 98.4, pulse 76, resp 14, BP 128/80. Weight 215 lbs. Labs: glucose 132 HgbA1C 6.6. Total cholesterol 232, Triglycerides 220, LDL 138, HDL 34. BUN 20, Cr 1.0, GFR 65. 1. What is the diagnosis? 2. What treatment is indicated? 3. Does he need any referrals? 4. What patient education should be given?
1. Diabetes (we have HgbA1C and fasting glucose >126) and hyperlipidemia 2. Metformin and a statin 3. Ophthalmology, podiatrist, nutritionist (or diabetic educator) 4. Glucometer: fasting goals should be less than 130, post-prandial less than 180
A 32-year-old G2P1 Native American presents to the GYN office for her prenatal visit. She is 20 weeks pregnant and has been doing very well. She has no concerns today. SLIDE 71 FINISH
1. GTT (1 hour for screening) 2. Positive test is over 3. Treatment:
A 62-year-old male presents to the office for 3-month follow-up of HTN and review of labs. He is currently taking HCT 25 mg daily for his blood pressure. Vitals today: 98.6, pulse 72, resp 14, BP 138/86. Labs reveal glucose of 115, Total cholesterol 240, Triglycerides 222, LDL 140, HDL 32. 1. How do we interpret the labs? 2. What are we concerned about? 3. What information do we need? 4. What should we do about it?
1. Is that a fasting sugar? Yes. Looks like metabolic syndrome (high BP, high triglycerides/cholesterol, impaired glucose tolerance). 2. Metabolic syndrome 3. Was it fasting (yes). Does he have central obesity? 4. Lifestyle modifications (diet, exercise) for metabolic syndrome. Stop HCTZ (can elevate blood glucose) and start ACEI. Order HgbA1C, BMP. See him back in 4-6 weeks.
A 30-year-old male presents to the office with polyuria, polydipsia, and polyphagia worsening over the past month. He has a family history of his mother having vitiligo and diabetes. Temperature is 97.8, pulse is 90/min, respirations are 18/min, and blood pressure is 120/76 mmHg. Height is 72 in and he weighs 164 lbs. BMI is 22.2. 1. What is the most likely diagnosis? 2. What labs will you order? 3. What treatment is indicated?
1. LADA: family history, symptoms, age, low BMI 2. Order HgbA1C, CMP, and islet cell antibodies and anti-insulin antibodies 3. Insulin (if diagnosed with LADA)
Metformin typically lowers the HgbA1C by _____________%
1.5-2
When using a short acting insulin like Humulin or Novolin R, when should this be taken?
30-45 mins BEFORE each meal It takes 1/2-1hr to work Peaks in 2-4 hours Lasts 4-8 hours
What type of medication is acarbose (Precose)?
Alpha glucosidase inhibitors
Which DM medication cannot be taken with alcohol?
Alpha glucosidase inhibitors (acarbose (Precose))
Presents for a routine follow-up. Has been taking Lisinopril 20 mg, metoprolol succinate 100 mg daily, metformin 500 mg BID (had to cut back d/t decreased GFR under 45), empagliflozin (Jardiance) 25 mg daily, dulaglutide (Trulicity) 1.5 mg SQ weekly, and atorvastatin 40 mg daily. Vitals: 98.0, pulse 62, resp 16, BP 126/80. Weight 234 lbs. Labs: Labs: glucose 202 HgbA1C 8.2. BUN 24 Cr 1.3 GFR 37. What treatment is indicated?
Assessment Plan: consider insulin, could add sulfonylurea
Presents for follow-up after discharge from hospital. He was admitted 5 days ago with a STEMI and had a catheterization with 2 stents placed. Has been taking Lisinopril 20 mg, HCT 25 mg, metformin 1000 mg BID, empagliflozin (Jardiance) 25 mg daily and atorvastatin 20 mg daily. Vitals: 98.6, pulse 70, resp 14, BP 130/82. Weight 227 lbs. Labs: Labs: glucose 156 HgbA1C 7.4. Total cholesterol 189, Triglycerides 134, LDL 90, HDL 38. BUN 21 Cr 1.25 GFR 47. What treatment is indicated?
Assessment: HTN, DM2 with nephropathy, Hyperlipidemia, CAD (aka ASCVD) Plan: Add beta blocker (HTN control) and GLP-1 agonist. Also add aspirin and Plavix.
Presents for follow-up. Has been taking Lisinopril 10 mg, HCT 25 mg, metformin 1000 mg BID, and atorvastatin 20 mg daily. Vitals: 98.2, pulse 76, resp 14, BP 138/86. Weight 225 lbs. Labs: Labs: glucose 175 HgbA1C 7.6. Total cholesterol 189, Triglycerides 134, LDL 70, HDL 38. BUN 20, Cr 1.2, GFR 55. Microalbulmin 100 mg (<30). What treatment is indicated?
Assessment: HTN, DM2, Hyperlipidemia Plan: Add GLP-1 (lose weight, helps sugars) or SGLT2 (helps BP, lowers sugar, weight loss, GFR/microalbumin is showing some nephropathy)
A patient 1 year s/p gastric bypass presents to the office after their most recent A1C came back elevated. After the surgery they were able to stop all DM medications. You want to start them on metformin. What do you need to supplement with if you do this?
B12
Why is it theorized that SGLT2s increase the risk of DKA?
Because SGLT2 inhibitors increase glucosuria and stimulate glucagon and lipolysis. This is primarily seen if you are sick and not eating/vomiting. If you are peeing out a lot of sugar (and already hypoglycemic) and using alternative energy sources as sugar, you increase ketoacids, which can lead to anion gap metabolic acidosis causing DKA.
When should meglitinides be taken?
Before each meal
What are the benefits of Mounjaro?
Best for weight loss
What are pharmacological treatments for DM2?
Biguanides (aka Metformin) GLP-1 receptor agonists SLGT-2 inhibitors DDP-4 inhibitors Secretagogues Thiazolidinediones Glucosidase inhibitors Insulin
Why are patients with CHF not supposed to take metformin?
CHF puts them at risk for lactic acidosis PLUS metformin puts them at higher risk (since the lactate cannot be broken down)
Type 1 diabetes needs both basal and bolus dosing. How can this be done?
Can be obtained either using 4 injections daily: •Basal replacement: glargine (Lantus/Toujeo) or dentimir (Levemir) •Rapid acting: lispro (Humalog), Aspart (Novolog), or glulisine (Apidra) given with each meal Can be obtained through a pump: •Small electronic device that delivers SHORT ACTING insulin •Delivers a basal rate •Can adjust bolus depending on carb counts
How do you choose second line meds for patients with DM and no history of ASCVD?
Choose the medication based upon drug effects and patient factors
What are contraindications of acarbose (Precose)?
Cirrhosis IBD Renal failure DO NOT TAKE WITH ETOH
What are GLP-1 and GLP-receptor agonists?
Combo of GLP-1 and Glucose dependent insulinotropic polypeptide Ex: Tirzepatide (Mounjaro)
What are the cons of insulin pumps?
Cost, battery powered, can dislodge
What are the benefits of sulfonylureas?
Effective (around as good as metformin at decreasing HgbA1C) Cost effective
What extra adverse effects is Canagliflozin associated with?
Elevated LDL and HDL Possible increased fracture and risk of amputations Should not be given to patients with severe hepatic impairment
When should Invokana be taken?
First thing in the morning on an empty stomach
What are side effects of alpha glucosidase inhibitors (acarbose)?
Flatulence GI upset
What are contraindications of biguanides (metformin)?
GFR < 30 (note: if GFR is 30-45, half dosing) because it will lead to lactic acidosis Severe liver disease Unstable CHF
Which medication classes can decrease AVCVF risk?
GLP-1 agonists SGLT2 inhibitors
Which sufonylureas are best to use in the elderly?
Glipizide (Glucotrol) Glyburide (DiaBeta/Micronase)
What is the first line medication for type 2 DM?
Glucophage (Metformin)
What are side effects of meglitinides?
HYPOGLYCEMIA (slightly less than sulfonylureas)
What is the primary pharmacological treatment for type 1 DM?
Insulin
Why can't patients with a personal or family history of medullary thyroid cancer or MEN take GLP-1 agonists?
It increases the risk of developing medullary thyroid cancer in these patients
When using long acting insulins like Lantus, Tougeo, Levemir, or Tresiba how long does it take for the onset of insulin to work? When does it peak? How long does it last? How often do you take it?
Lantus: 1 hr, lasts up to 24, take daily Tougeo: 1-4 hrs, lasts longer than 24 hrs, take BID Levemir: 30-90 mins, lasts 12-20 hrs, take daily Tresiba: 30-90 mins, lasts up to 42 hrs, take daily Minimal to flat peaks for all
What are the benefits of GLP-1 agonists?
Lowers HgbA1C (around 0.5-1.5%) Weight loss Lipid and blood pressure reduction •Liralgutide, semaglutide, dulaglutide decrease cardiovascular risk esp. with known atherosclerotic cardiovascular disease (heart attack pts) •Liralgutide decreases nephropathy
What are the side effects of DPP-4 inhibitors?
MINIMAL •URI symptoms/headaches •Joint pain •Pancreatitis (the Ps) •saxagliptin (Onglyza) and alogliptin (Nesina): increased risk of CHF •Alogliptin (Nesina): increased LFTs •? Impact on immune system
What are signs of lactic acidosis?
Malaise Myalgias Respiratory distress Somnolence Abdominal pain
What medications would you discontinue in a type 2 diabetic that you need to start on insulin?
Meds that would cause hypoglycemia: Meglitinides Sulfonylureas
Which oral DM medications can cause hypoglycemia?
Meglitinides Sulfonylureas
What class of medication are the "linides"?
Meglitinides ex: •repaglinide (Prandin) and nateglinide (Starlix)
How are sulfonylureas metabolized and secreted?
Metabolized by the liver and cleared by the kidneys
What is the issue with metformin and IV contrast?
Metformin decreases the metabolism and secretion of lactate which increases the risk of lactic acidosis HOLD FOR 48 HOURS
When treating DM type 1, how is insulin used?
Need both basal and prandial (bolus) coverage
What type of GLP-1 agonist is semaglutide (Rybelsus)?
Oral
A patient is taking metformin. What would put them at increased risk for lactic acidosis?
Radiology contrast Renal failure Age >65 Dehydration Sepsis Hepatic failure Unstable CHF Excessive alcohol intake Use with carbonic anhydrase inhibitors (ie Topamax)
What are contraindications of sulfonylureas?
Renal or hepatic failure
What are indications to use repaglinide (Prandin) and nateglinide (Starlix)?
Repaglinide (Prandin) is okay to use with renal railure Nateglinide (Starlix) is okay to use with hepatic failure
How long do different types of insulin last? What is the difference in peaks?
Short acting meds like aspart, glulisne, lispro peak fast and dont last long. These are good for covering meals only. Intermediate meds like NPH last 12-16 hours, take longer to peak, and don't have as high of a peak. Long acting meds like detemir (Levimir) and glargine (Lantus) last longer and do not peak. These are for basal rates of insulin.
What meds are the -gliflozins?
Sodium-glucose co-transporter 2 inhibitor (SGLT2 inhibitors) Ex: empagliflozin (Jardiance), dapagliflozin (Farxiga), canagliflozin (Invokana), ertugliflozin (Steglatro)
How are sulfonylureas dosed?
Start low, titrate up Huge window
How is Mounjaro dosed?
Start low, titrated up until goal is reached
How are DPP-4 inhibitors dosed?
Start with the highest dose (lower doses are renal doses). Not titrated, no adding more. It is just the highest dose (unless renal problem)
What type of GLP-1 agonists are dulaglutide (Trulicity), semaglutide (Ozempic), and Bydureon?
Sub Q Long acting (Bydureon is a once weekly injection of exenatide) *These are used more commonly because they are all once weekly!!
What type of GLP-1 agonists are exenatide (Byetta) and liraglutide (Victoza)?
Sub Q Short acting
What class of medication are the "-ides"? Examples?
Sulfonylureas Ex: glipizide (Glucotrol), glyburide (DiaBeta/Micronase) and glimepiride (Amaryl) Glipizide/glimeperide shorter acting less hypoglycemia, better in the elderly
When using intermediate insulins like NPH or Novolin N, when is this used? When does it start working, peak, and how long does it last?
Taken BID or HS 1-2 hours to start working "Peaks" within 4-12 hours Lasts 14-24 hours
When should acarbose be taken?
Taken three times daily with the first bite of food
Are once weekly or once daily GLP-1 agonists better?
The once weekly injections have better results
How are medications like humulin/NPH 70/30 and Novolin R/NPH used?
They are only used for DM2 They are Basal+Bolus insulin that are taken 30-45 mins before breakfast and dinner This limits the amount of injections needed
How is GLP-1 agonists dosed?
They are titrated up until the patient is at goal or at max dose
Why don't we prescribe DPP-4 inhibitors and GLP-1 agonists together?
They basically do the same thing and doing this won't have added effect The end effect of both is to increase GLP-1 (which has great effects)
What is the MOA of Mounjaro?
This is a GLP-1 and GLP-receptor agonist combo •GIP produced in the K cells of small intestine •Incretin effect: glucose dependent insulin secretion •Works on pancreatic beta and alpha cells •Stimulates glucagon during euglycemia/hypoglycemic states •No effect on glucagon in hyperglycemic states •Less effect on gastric emptying
What are the cons of GLP-1 agonists?
Very expensive (like $700/mo for 4 shots)
When using a rapid acting insulin like Humalog, Novolog, or Apidra, when should this be taken?
WITH each meal (this mimics what the body should be doing when you eat) It starts working within 10-20 mins Peaks within 1-3 hrs Lasts 3-5 hours
What are the benefits of biguanides (metformin)?
Weight loss Rarely causes hypoglycemia Improves lipid profile Possible decreased macrovascular risk Cheap
Can empagliflozin be used in those with hepatic impairment?
Yes (just not severe)
What are examples of GLP-1 agonists?
the -tides: Sub-q injections: •Short acting: exenatide (Byetta), liraglutide (Victoza) •Long acting: dulaglutide (Trulicity), semaglutide (Ozempic), exenatide once weekly (Bydureon) Oral •Semaglutide (Rybelsus)
What are common needle sites for an insulin pump?
•Abdomen, upper buttocks, hip •Needs to be at least 2 inches from umbilicus •Change every 2-3 days in a rotating pattern
When using insulin to treat DM2, how is it used?
•BASAL rate supplementation with insulin and •Continued use of SOME ORAL AGENTS to control postprandial glucose load (just not ones that cause hypoglycemia)
How does acarbose (Precose) work?
•Decrease carbohydrate absorption in the GI tract •Does not affect glucose utilization or insulin secretion
How does Metformin work?
•Decreases hepatic gluconeogenesis •Increases peripheral glucose utilization •Decreases insulin resistance •Lowers serum free fatty acids •Not metabolized; excreted unchanged through the kidneys Does NOT affect the pancreas (unlike a lot of other meds and RARELY causes hypoglycemia because of this)
What are the main lifestyle modifications that need to be implemented with DM?
•Diet: Referral to nutritionist Exercise: •150 minutes/week of moderate activity •Decreases cardiovascular risk, lower blood pressure, maintain/build muscle mass, lower body fat •Weight loss •Diabetic education classes
What dietary modifications are recommended for diabetes?
•Fruits and vegetables •Lean meats and plant-based sources of protein •Less added sugar •Less processed foods •Sugar free and fat free does NOT equal healthy
What are the side effects of Biguanides?
•GI (#1 complaint) •N/V/D, flatulence, indigestion, abdominal pain, anorexia (diarrhea is the #1 complaint) •GI side effects are dose dependent •Lactic acidosis (most serious) •Reduces absorption of B12 (gastric bypass increases risk) •Headache
What is the mechanism of action for GLP-1 receptor agonists?
•GLP-1 is produced in the L-cells in the small intestine and is secreted in response to food (sugar) • GLP-1 exerts its main effect by stimulating GLUCOSE DEPENDENT insulin release from the pancreatic beta cells •Glucose-dependent insulin secretion means no hypoglycemia (only released when there is lots of sugar!) •Slows gastric emptying •Reduces postprandial glucagon release •Reduces of food intake
What are the second line meds (after metformin) for people with DM that have known ASCVD?
•GLP1: liraglutide, dulaglutide , semaglutide: proven reductions in cardiovascular mortality •SGLT2: empagliflozin (Jardiance): also decreases hospitalization from CHF and progression of nephropathy
What are side effects of SGLT2 inhibitors?
•GU infections •Hypotension •Acute kidney injury •Fractures •DKA •Increased risk of amputations •Fournier's gangrene (very bad necrotizing infection of perineum)
How do DPP-4 inhibitors (-agliptins) work?
•Glucagon-like peptide-1 (GLP-1) is produced by L-cells in the small intestine and is secreted in response to food • GLP-1 stimulates GLUCOSE DEPENDENT insulin release from the pancreatic beta cells and decreases glucagon from alpha cells •Slows gastric emptying, inhibit inappropriate post-meal glucagon release, and reduce food intake •DPP-4 is an enzyme expressed on the surface of most cell types that deactivates insulinotropic polypeptide (GIP) and GLP-1 By blocking DPP-4, more GLP-1 is able to slow gastric emptying, lower blood glucose (increase insulin), stop the release of extra sugar (stop glucagon release) and create feelings of satiety.
What are side effects of sulfonylureas (-ides)?
•HYPOGLYCEMIA •Weight gain •Nausea •Mild photosensitivity •Increase LFTs
What are contraindications of GLP-1 agonists?
•Hx of pancreatitis, severe renal impairment, confirmed gastroparesis (think about the side effects) •Liralgutide, albiglutide, dulaglutide: personal or family hx of medullary thyroid cancer or MEN (multiple endocrine neoplasms) •Caution in patients with GFR < 30 •Do not use exenatide with a GFR<30
When should insulin be initiated for a type 2 diabetic?
•Initiate if HgbA1C is ≥ 9% with symptoms •Add if not at goal with multiple oral medications •Start with basal insulin •Glargine (Lantus) or detemir (Levemir) •Use with metformin and GLP-1, +/- SGLT2
What meds can you use in stage 4 CKD?
•Insulin •Glipizide (Glucotrol) •repaglinide (Prandin) •linagliptin (Tradjenta)
What does MyPlate recommend?
•Majority of plate should be non-starch vegetable •Smaller serving of whole grains (starch) •Lean protein •Non-processed fruits •Add a serving of low fat milk 9" plate
What are the AACE goals for the treatment of DM2?
•Minimizing hypoglycemia is a priority •Minimizing weight gain is a priority •Safety and efficacy outweighs cost of medication •Must evaluate effectiveness of therapy frequently until stable •Rapid acting insulins are superior to regular insulin •Long acting insulin analogs are superior to NPH-insulin •Individualize therapy •Strong focus on lifestyle modification and risk reduction
What are side effects of GLP-1 agonists?
•N/V/D •Pancreatitis (the P meds) •Gallbladder disease •Delayed gastric emptying •Injection site reaction (rotate where they give shots) •More common with long acting •Semaglutide (Ozempic) has increased diabetic retinopathy
What are side effects of Tirzepatide (Mounjaro)?
•N/V/D/C •Gallbladder disease •Pancreatitis (the P meds, its a GLP-1 and GIP combo) •Injection site reaction •AKI •Increased heart rate •Can worsen diabetic retinopathy •Contraindicated personal/family hx medullary thyroid cancer
What are the benefits of DPP-4 inhibitors?
•No hypoglycemia •Weight neutral •linagliptin (Tradjenta) can be used with decreased GFR
How does GFR affect the dosing of dapagliflozin (Farxiga)?
•Renal dosing for DM: avoid with GFR <45 for glycemic control (it won't have the intended effect on the DM if the GFR isn't high enough) •For decreasing nephropathy avoid GFR < 25 (it will protect against nephropathy, still won't help get rid of sugars)
What are contraindications of SGLT2 inhibitors? When can they be used with caution?
•Renal insufficiency •Dapagliflozin (Farxiga): active bladder cancer •Type 1 DM: use with caution, risk of DKA •Prior DKA Use with Caution: •Frequent UTIs •Osteoporosis and high risk of falls •Foot ulcerations •Predisposing factors for DKA
How do SGLT2 inhibitors work?
•SGLT2 is expressed in the proximal tubule and mediates reabsorption of approximately 90 percent of the filtered glucose load •SGLT2 inhibitors inhibit SGLT thus promoting renal excretion of glucose
How do you reduce the risk of DKA if a patient is on a SGLT2 inhibitor?
•STOP at lease 24 hours prior to surgery (some say 72 hrs) and extreme sports •Hold 2 days prior to colonoscopy • Avoid very low carb diet and excessive alcohol
How do sulfonylureas (-ides) work?
•Secretagogue • Stimulates the beta cells in the pancreas to secrete more insulin (GLUCOSE INDEPENDENT) •Metabolized by the LIVER and cleared by the KIDNEYS
What is the MOA of meglitinides?
•Short-acting insulin secretagogues, similar to sulfonylureas but acts through a different receptor to cause increased insulin secretion •GLUCOSE INDEPENDENT
What are the benefits of SGLT2 inhibitors?
•Weight loss, lowers blood pressure •Limited hypoglycemia •Empagliflozin and canagliflozin lower cardiovascular risk in patients with known ASCVD (Empagliflozin preferred medication) •All have some data that they decreased risk of hospitalization for heart failure and progression of nephropathy •Note with nephropathy benefit in those with higher GFRs
What are contraindications of meglitinides?
•repaglinide (Prandin) hepatic insufficiency •nateglinide (Starlix) renal insufficiency
What is the ADA method of dieting?
•½ plate non-starchy vegetables •¼ plate: lean protein •¼ plate carbohydrates •Includes fruit and dairy
