More info on Diabetes

By Anais Carbonell, M.D.

GUIDELINES FOR THERAPY

· Type 1 diabetics need both Long acting and short acting ALWAYS and they should be managed by an endocrinologist, the guidelines below are for Type 2 diabetics managed in the PCP setting.

· If the a1c at diagnosis is <9% you can trial oral drug therapy alone, if above nine you should really start insulin

· OUTPATIENT: FBG target: 100-110, adjust long acting insulin to get to this target FIRST and then if A1c remains elevated target the post prandial glucose with short acting insulin. Goal a1c if patient age <65 is 6.5% or less (old guideline was 7)

· BMI above 35 can consider gastric bypass

· Goal BP is <130/80

· For lipids, goal LDL <100 if no other risk factors, <70 if risk factors for heart disease present and <55 if there are clinical risk factors for heart disease

· They need an eye exam every year starting with diagnosis, monofilament exam yearly as well

FIRST LINE FOR A1C<7.5% FOR MONOTHERAPY

DUAL THERAPY: For A1c>7.5 at start, use metformin PLUS one of the agents below

A1c >9%: Initiate insulin at diagnosis if symptomatic or amenable, at least trial dual or triple therapy from the options listed below if not amenable for insulin

Drug	MOA/Uses	Contraindications	Brand Names
Metformin	Reduces insulin resistance moderately and decreases gluconeogenesis	eGFR<45 (It is really <30 however use extreme caution <45)	***FREE AT PUBLIX*** If GI upset is an issue can order the SA (sustained release) form with the VA, not free at Publix.
SGLT-2i	Promote the renal excretion of glucose by blocking the SGLT2 in the proximal tubules which causes renal absorption of glucose. Also decrease BP and help with weight loss. Note that you should cut BP meds and diuretics in half when starting this.	Caution in people with recurrent UTIs or yeast infections (obese women or uncircumcised men). Tell females to use baby wipes.	1. Dapagliflozin (Forxiga) QD 2. Canagliflozin (Invokana) QD 100 mg or 300 mg max. Comes in combo pill with metformin and causes the most excretion of sugar of the 3. 3. Empagliflozin (Jardiance) QD – Reduces CV risk! Secretes 300-400 calories of sugar daily.
DPP-4i	Inhibit the DPP-4 enzyme which is the enzyme that naturally degrades GLP-1. Also increases production of insulin and decreases production of glucagon. Weight neutral.	OK to use with gastroparesis because does not delay gastric emptying. Cannot use with history of pancreatitis and cannot be used with GLP-1 receptor agonists due to pancreatitis risk	1. Sitagliptin (Januvia) QD 2. Saxagliptin (Onglyza) QD 3. Linagliptin (Tradjenta) QD – better in CKD because primarily excreted by the liver 4. Alogliptin (Nesina) QD: OK to use in HD/CKD
Agi – No one uses these		Causes flatulence and bloating	1. Acarbose
TZD – not recommended		Can cause or exacerbate CHF so do not use with CHF patients	1. Pioglitazone – start at 15 mg and increase in 15 mg increments to 45 mg/day max.
Sulfonylureas	SUs cause pancreas to secrete insulin and is associated with hypoglycemia		1. Glyburide – renally excreted, max 20 mg daily 2. Glipizide (glucotrol)– both renally and hepatically excreted, 10-20 mg BID 3. Glimepiride – hepatically excreted, 1-8 mg QD dosing
GLP-1 Receptor agonists – Incretin (Injection)	Bind to GLP-1 receptors and stimulate glucose dependent insulin release from the pancreatic islet cells. the short acting ones have a greater effect on post prandial hyperglycemia and gastric emptying rather than fasting glucose. Associated with weight loss but causes nausea. Decreases glucagon and appetite.	Do not combine with DPP-4 Inhibitors because this can cause pancreatitis. All except for the short acting (lixisenatide and exenatide) are contraindicated in MEN. *Cut the meal time insulin when adding this* DO NOT use with gastroparesis! Exenatide CANNOT be used with CKD but all of the others can, even with HD. Cannot use with MEN syndrome.	1. Exenatide: BID (Byetta) given 30 minutes before a meal or qweekly (Bydureon) but the qweekly one has microspheres which causes bumps under the skin and patients don't like and Bydureon also takes 6 months to take a full effect, but better SE than Byetta. Neither can be used with CKD because renally excreted! 2. Liraglutide (Victoza): QD. Preferred if MI or stroke for secondary prevention. 3. Albiglutide (Tanzeum): Qweekly. Less nausea but also less weight loss. Takes 15 minutes to mix. Approved for use along with basal insulin 4. Lixisenatide (Adlyxin): QD at any time of day 4. Dulaglutide (Trulicity): qweekly autoinjector that is super easy to use. 0.75 or 1.5 mg dosing, no measuring 5. Ozempic (semaglutide): Qweekly injection, BETTER weight loss than trulicity

*Consider adding mealtime insulin or GLP1 when the patient has uncontrolled DM with high post prandials, A1c>9 with basal at target, A1c<8.5 but post prandials remain elevated. Note that you can use mealtime insulin AND the GLP1s together for tighter post prandial glucose control but cannot use both with the DDP4 because of risk of pancreatitis.

TYPES OF INSULIN

Long Acting Insulin	Advantages	Notes
Insulin degludec (tresiba)	Can be administered at any time of day QD. Half life of 42 hours. Pen goes up to 160 units.	Associated with weight gain. Note that it comes in a u100 pen (80 units) or u200 pen (160) units but note that the u200 pen must be dosed in increments of 2 (no odd number dosing)
Insulin Glargine (Toujeo) - basically its lantus u300	3x as concentrated as lantus and lasts 36 hours. QD dosing, pen goes up to 80 units. Not as much weight gain with this, less risk of hypoglycemia as well
Insulin Glargine (Lantus) - solostar pen is not that easy to use and only goes up to 80 units	No peak, lasts almost 24 hours, QD dosing but can split into BID dosing if patient taking >50 units per day	Associated with weight gain. Dose in 70/30 split, 70% LA with 30% SA
Insulin detemir (Levemir) - inferior to lantus but cheaper	Weight neutral. States that its 24 hours but not really, better when dosed BID because the half life is lower with lower doses	You need more units of levemir than lantus to achieve the same effect on blood sugars.
NPH (human)	Peaks in 12-16 hours	BID dosing

*If basal dose is 40-50 units and the patient continues to have high post prandial glucoses, start adding short acting insulin with meals

*Only use combo pens with both short acting and long acting for convenience (like nursing homes) because BID dosing.

*Lilly pens and humolog quikpens are not that easy to use because the back of the pen comes up with units so harder to press, the novo flexpens are the easiest to use (these include the levemir, novolog and tresiba)

Short Acting Insulin	Advantages/Uses	Notes
Regular Insulin	Half life of 4-6 hours, good for use in gastroparesis but must be given 30 minutes before meals	Increasing the dose increases the duration of action so higher doses have an increased risk of hypoglycemia
U500	Pen goes by units of 5, up to 300 in one pen. Give BID and it is so long lasting because of the high dose it functions as your short and long acting insulin	DO NOT PRESCRIBE THIS – this must be managed by endocrine given complex dosing
Novolog (Aspart)	Give 15 minutes before meals, duration not affected by dose	Novo pen is easier to use than humolog (Lilly) pen
Humolog (Lispro)	Give 15 minutes before meals, duration not affected by dose
Glulysine (Apidra)

INPATIENT DIABETES MANAGEMENT

· Goal blood sugars while inpatient is 100-140 fasting, 100-180 postprandial; it is better to use a low-dose long-acting insulin than sliding scale insulin

· Long-acting insulin should be decreased by 25-50% the night before or morning of surgery. Short acting insulin should be held until the patient resumes oral intake after surgery. All oral diabetes medications should be held the morning of surgery.

MISCELLANEOUS PEARLS

· Symogi: Hypoglycemia with morning reactive hyperglycemia, decrease nighttime insulin. They will usually report hypoglycemia or parasomnias

· Insulinoma or sulfonylureas: Hypoglycemia with high C peptide. Also test the urine for sulfonylureas to make sure that patients are not over dosing on SUs.

o On boards they will give you a patient with neuro signs that improve when they eat. Admit them for a 72 hour fast and then collect the tests when they are hypoglycemic.

· Extra exogenous insulin: C-peptide low