Possibilities today...Treatments Tomorrow | |
- NORCAL MEDICAL RESEARCH -
JUNE 2024 NEWSLETTER
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Hello friends and welcome to the NorCal Medical Research June newsletter!
While summer is upon us and vacation is top of mind for many, we are keeping busy at NorCal and excited to share updates on our current and upcoming clinical trials.
Coming in the early fall, we will be conducting a new weight loss study for patients with type 2 diabetes. Read on for the study's details below and for my analysis of the new weight loss drugs overall in the “Back to the Future” section. I included some info on how these drugs were discovered, how they work, their incredible current successes as well as a look at current concerns about their long-term use, side effects and some of the ways to reduce complications. I have been very involved in clinical trials with this group of medications for three decades and I believe it’s more critical than ever to continue to get the answers we need by conducting careful ongoing clinical studies as we gain real world experience.
An important note, the recent Lilly weight loss study investigating another glucoregulatory hormone similar to GLP-1 filled very quickly and is now closed to further enrollment.
There is so much buzz about these weight loss medications that are producing unprecedented weight loss in increasing numbers of people, that we encourage you to contact us immediately when you are interested in a study or have a friend or loved one who might be. Call us if you want to get on a waiting list to make sure you can get screened and get information while space is available.
Currently we are still seeking persons with Type 2 Diabetes at high risk but not optimally controlled on oral meds alone, to participate in an important Lilly Diabetes Study comparing addition of new oral GLP-1 to basal insulin to improve control. Eligible patients need to have a history of either mild to moderate chronic kidney disease or a cardiovascular (CV) risk. Outcomes of glucose control, A1C, weight and cardiovascular events will be closely followed for the duration of the trial with the goal of improving glucose control and reducing CV risks for all participants.
In addition we are enrolling patients in a Thyroid Study which compares animal derived thyroid supplement as Armour (T3/T4) to synthetic thyroid hormone levothyroxine (T4) as treatment for hypothyroidism.
We are also screening individuals with either Type 1 or Type 2 Diabetes for a Diabetic Peripheral Neuropathy study (DPN)) to evaluate a new oral pain relief medication for persons with moderate to severe painful diabetic neuropathy. This is our second study with this promising non-opioid pain reliever. DPN is a serious problem for patients and there are few effective treatments!
You can find further details about these currently enrolling studies below.
Thank you for supporting our mission to improve patient outcomes through careful data gathering and clinical research at our site right here in Marin. We need to get the word out about our work so that everyone gets an opportunity to explore the opportunities and everyone is represented!
Please also contact us at 415-461-1585 or info@norcalmedicalresearch.com with any questions.
In health,
Dr. G
Linda Gaudiani MD FACE FACP
Medical Director
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We try to get our exercise time in after meetings on Fridays!
From left to right: Dr. Irene Teper, Dr. Linda Gaudiani and Dr. Elizabeth Lowe
Click here to get acquainted with our physicians and here to meet the rest of our staff.
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The Abbvie Thyroid Study will compare the use of a purified naturally derived thyroid replacement therapy, Armour thyroid, to synthetic levothyroxine. Armour is made from purified porcine thyroid and contains both T4 and T3 thyroid hormones.
This study will investigate dose equivalents of LT4 (levothyroxine) and Armour so that individuals can be safely converted from one to the other. All participants will start on the Armour thyroid and then will be randomized to receive either LT4 synthetic or Armour T3/T4.
WHO IS ELIGIBLE TO PARTICIPATE?
You may be eligible to participate if you:
- Are 18 to 75 years of age
- Are diagnosed with primary hypothyroidism for at least one year
- Have had no thyroid surgery within past 12 months
- Have been on continuous thyroid replacement therapy with LT4 for last 6 months
- Have had a normal TSH in the past year
The duration of the study will be one year.
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DIABETIC PERIPHERAL NEUROPATHY (DPN) STUDY | |
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NorCal is currently screening patients for a short- term study to further extend the data already existing for an investigational drug developed specifically to reduce pain related to DPN. This study might be right for you if you experience inadequate pain relief from your DPN.
This trial will study the efficacy and side effects of the investigational drug, LX9211, which works by blocking AP2-associated protein kinase 1 which is thought to be involved in nerve pain. This is the second study we have done on this drug which showed efficacy in earlier trials.This trial will further study optimal dosages.
You may qualify to participate if you:
- Are 18 years or older
- Have type 1 or type 2 diabetes
- Have an A1C less than or equal to 11%
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Have ongoing diabetic peripheral neuropathy with moderate to severe pain ·of approximately 5 or more on a scale of 1 to 10
Your medical history and other criteria will be checked to determine if you can take part in the study.
The study will last about 16 weeks.
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This Lilly study will test the safety and efficacy of a new oral GLP-1, Orforglipron, compared with basal insulin therapy (glargine). No placebo.
The goal is to compare the effect of treatment on HBA1c and cardiovascular outcomes over 24 months.
You can join this study if you:
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Are aged 18 years or over
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Have type 2 diabetes and are taking at least one medicine to manage your diabetes
- Have a BMI of 27 or higher
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Have or are at risk of heart disease, stroke, or other blood vessel diseases, or
- Have kidney disease
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NEW WEIGHT LOSS STUDY – COMING EARLY FALL | |
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The study will test an investigational medicine to see if it can safely reduce weight in people with excess weight and type 2 diabetes.
You can join this study if you:
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are aged 18 years or older
- have type 2 diabetes with an HbA1c of 7.0 to 10.5
- have excess weight with a BMI of 30 or more, or a BMI of 27 or more and 1 of the following: high blood pressure, abnormal cholesterol levels, sleep apnea or heart disease.
Patients can be entered if they meet all criteria including pre-trial treatment with diet and exercise alone, or Metformin with or without an SGLT2 inhibitor. Only oral medications for diabetes are allowed. Use of insulin or GLP-1 medications at entry is not allowed.
We will start screening patients for this new weight loss study about Labor Day.
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As with all clinical studies, participants will not have to pay for the study drugs, study visits, or for the procedures or tests that are needed as part of these studies. Additionally, you may be compensated for your time and reimbursed for approved, study-related travel.
Please contact us at 415-461-1585 or info@norcalmedicalresearch.com with questions.
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- NORCAL KNOWLEDGE NUGGETS - | |
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THE GLP-1 WONDER DRUGS
BACK TO THE FUTURE
The new weight loss drugs belong to a class of pharmaceuticals known as “GLP-1 agonists, or stimulators," that has revolutionized obesity treatment by offering a completely new way to address this condition. These drugs were originally developed to control diabetes and the first such drug was approved by the FDA in the 1990s! Several others were approved as well for the treatment of type 2 diabetes.
The weight loss potential of these drugs took center stage only in the past three years, after an early clinical trial of Ozempic confirmed a surprising benefit; in addition to improved diabetes control those taking it could lose as much as 15% of their body weight. Social media caught on, use of the drugs by celebrities like Elon Musk and Oprah and deft marketing by Novo Nordisk, Ozempic’s manufacturer, did the rest. The new generation of GLP-1 agonists on the market, Novo Nordisk’s Ozempic, Wegovy, and Rybelsus (the only pill form) and Eli Lilly’s Mounjaro and Zepbound, have now become household names and are producing unprecedented weight loss in increasing numbers of people. It is estimated that over 9 million prescriptions have been written! While Ozempic, Rybelsus and Mounjaro are approved to treat diabetes, in practice doctors also prescribe these drugs to patients who do not have diabetes looking to lose weight .
Wegovy, Rybelsus and Ozempic contain the compound semaglutide, which stimulates levels of the body’s hormone GLP-1, and they work by slowing down gastric and bowel activity, by reducing the appetite centers in the brain, and by stimulating insulin production by the pancreas. This makes people feel full faster, and for longer. Mounjaro and Zepbound work similarly, but they use tirzepatide which stimulates both GLP-1 and a second similar gut hormone, GIP.
Semaglutide and tirzepatide target the brain directly and curb hunger, appetite and craving signals, silencing what many users have called “food noise.”
These drugs don’t work for everyone and in clinical trials a small fraction of participants does not lose significant weight or see meaningful improvements in blood sugar control. But for most patients, the medications can be strikingly effective with losses of 10-25% of body weight.
Clinical trials have also found these drugs protect against heart disease with a reduction in overall risk in people without diabetes of 20% in the case of semaglutide and they can also reduce kidney disease, fatty liver disease and heart failure in both persons with and without diabetes. The GLP-1 drugs are now being tested for a myriad of other unrelated disorders including Parkinson's, addiction disorders and others.
Overall, these medications are well tolerated by most patients, especially if carefully prescribed and monitored, but there are some risks and side effects associated with both short- and long-term use to be aware of. Long term as many as 10-30% of patients discontinue drug treatment in clinical trials!
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MOST COMMON SIDE EFFECTS
Patients tend to experience most side effects when they first start their treatment or as they increase their doses over the first few months. The most common issues are gastrointestinal: nausea, vomiting, diarrhea, constipation, acid reflux, stomach pain and discomfort. People can also experience fatigue, dizziness and headaches.
To avoid nausea, I advise patients to halve their portion sizes immediately upon starting the drug and not wait until they are feeling full to stop eating. Whatever they normally eat, patients should cut portions in half to start out and see how they do. This helps with their delayed gastric emptying and decreased motility, giving their gastrointestinal tract a chance to adjust. Also, not all patients require the maximum dose, so starting on a low dose and slowly increasing to an effective dose will help reduce chances of getting nausea. For similar reasons patients starting these medications should be advised to eat more slowly, and to stop eating as soon as they are no longer hungry, instead of when they feel full. Occasionally antinausea meds are helpful, dose reduction or drug holidays can also be used to help patients adjust. Avoiding fatty rich foods may also improve tolerance.
Regarding constipation, increasing fiber and fluid intake can be very helpful. Occasionally other supplements like psyllium and softeners are helpful.
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Losing a lot of weight quickly can also have ripple effects. Some patients note hair loss, although this can happen with large weight loss from other causes as well. Concern has arisen about the proportion of the lost weight that is fat mass vs lean body mass in patients taking these drugs. This is being studied more closely and new drugs are being designed that might reduce muscle mass loss.
It is important to note that loss of lean mass is expected with all weight loss interventions, including drugs, bariatric surgery or even intense lifestyle interventions. It’s not clear what long-term effect that may have on physical function, bone density, and longevity, and is of greatest concern in older adults with age-related low muscle mass obesity who are at risk for further muscle atrophy and frailty.
As such, clinician-supported weight loss plans should be tailored to the individual and include strength assessments and a comprehensive plan to address these concerns as well as recommendations for improving nutrition and exercise to minimize muscle loss.
This concern has led some drug companies including Eli Lilly, which makes Mounjaro and Zepbound, and others to develop combination treatments to build on the benefits of GLP-1 meds to help patients lose more fat while preserving, or even gaining, muscle.
REASSESSING RISKS OF GI COMPLICATIONS
Some earlier studies suggested GLP-1 receptor agonists might cause an increased risk for acute pancreatitis, but real-world studies and clinical trials are increasingly suggesting there is no significantly increased risk. The new data did, however, reinforce an association between GLP-1s and gastroparesis and biliary disease, specifically gallstones.
Although the weight loss results are stunning, these drugs are still being tested and studied and there is still some uncertainty about the potential side effects of their prolonged use over many years.
There are also concerns about possible effects on the bowel which could alter recommendations for patients undergoing elective surgery requiring anesthesia. Much more data will need to be reviewed before experts agree on recommendations so be sure to ask your doctors for specific advice in these situations.
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IMPORTANCE OF LIFESTYLE CHANGES TO AVOID REGAINING THE WEIGHT
We face many unknown questions about whether these drugs need to be continued permanently to maintain lost weight or whether some patients may be able to eventually be taken off these drugs with continued weight maintenance. This is another area of active clinical research.
A combination of support in making lifestyle changes and slow tapering may allow some patients to avoid regaining weight after coming off semaglutide but so far a number of studies show rapid regain.
Management of obesity is complex and multifaceted. Clinician supervised weight loss using medications should provide a comprehensive approach to mitigate any side effects. Education, anticipatory counseling, dietary education and physical activity counselling may also provide keys to success.
COST AND AVAILABILITY ISSUES
When these drugs work, they can be life-changing for people whose weight increases their health risks, from diabetes to heart, kidney and liver disease. Many patients have struggled for years with obesity and found that changes to diet and exercise just aren't sustainable on their own.
Yet Novo Nordisk and Lilly can't make enough GLP-1s to meet demand, and mostly sell them in a few of the world's wealthiest countries. Since so many people are turning to these drugs for weight loss alone, there are now shortages and new insurance hurdles for the diabetes patients who need them for glucose control as well.
In addition to the shortage of these medications, U.S. prices, often set above $1,000 per month without insurance, place them beyond the reach of many patients who need them.
Doctors are frustrated: they can’t get the medications for their patients, because they’re in shortage or insurance won’t cover them.
Unfortunately, as patients and practitioners contend with shortages and sky-high prices, con artists are filling the void with untested look-alikes and counterfeits. The website market is now flooded with fraudulent products sold without prescription, without FDA approval or even input from a licensed practitioner.
People seeking cheaper GLP-1 products should be wary of health clubs, medical spas, compounding pharmacies, weight loss clinics and online sites that are selling “compounded” versions of GLP-1 drugs which they tout as “generic versions.”
While it may be very tempting to buy these discounted drugs, generally, if it sounds too good to be true, it probably is!
NEW ORAL WEIGHT LOSS DRUGS: WHERE ARE WE AND WHAT’S NEXT?
Now that semaglutide and tirzepatide and other injectables have created a huge market for weight loss drugs, biotech and pharmaceutical companies are moving forward with oral formulations, which promise a greater level of convenience, in line with patient preference.
Many drugs are in various stages of development and submission for regulatory approval.
NorCal, formerly known as Marin Endocrine Care and Research, under my Medical Direction, has been actively involved in studying this class of medications in our clinical trials along with various leading pharmaceutical companies since the early 1990’s. We have a very deep history and experience that continues to the present in the area of weight loss medication research. We are now taking part in the five-year cardiovascular trials for tirzepatide and have studied many other GLP-1s. NorCal recently enrolled patients in a new trial studying an oral GLP-1, orforglipron, in persons without diabetes and we are now enrolling another for patients with high risk T2D with this oral GLP1. Early this fall we will open a weight loss study using two glucoregulatory hormones stimulators in combination to minimize doses and side effects. As always in clinical studies, proof of safety, efficacy and tolerance must come first.
We feel fortunate to be at the forefront of research in this exciting field that is improving the lives of so many people and teaching us a great deal more about obesity, diabetes, and metabolomic syndromes.
Without your participation, however, this progress would be impossible! Thank you!
SOURCES:
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Contact us at (415) 461-1585 or Info@NorCalMedicalResearch.com with any questions or feedback. We'd love to hear from you. Please share this newsletter with anyone you think might benefit from receiving it and finding out about our work.
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From left to right: Carol Singh, Jesse Cardozo and Dr. Linda Gaudiani | |
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